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1. Author Correction: Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials

Author

Ahani, Bahar, Tuffy, Kevin M., Aksyuk, Anastasia A., Wilkins, Deidre, Abram, Michael E., Dagan, Ron, Domachowske, Joseph B., Guest, Johnathan D., Ji, Hong, Kushnir, Anna, Leach, Amanda, Madhi, Shabir A., Mankad, Vaishali S., Simões, Eric A. F., Sparklin, Benjamin, Speer, Scott D., Stanley, Ann Marie, Tabor, David E., Hamrén, Ulrika Wählby, Kelly, Elizabeth J., and Villafana, Tonya

Published
2024
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3. Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials

Author

Ahani, Bahar, Tuffy, Kevin M., Aksyuk, Anastasia A., Wilkins, Deidre, Abram, Michael E., Dagan, Ron, Domachowske, Joseph B., Guest, Johnathan D., Ji, Hong, Kushnir, Anna, Leach, Amanda, Madhi, Shabir A., Mankad, Vaishali S., Simões, Eric A. F., Sparklin, Benjamin, Speer, Scott D., Stanley, Ann Marie, Tabor, David E., Hamrén, Ulrika Wählby, Kelly, Elizabeth J., and Villafana, Tonya

Published
2023
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4. An Antigenically Diverse, Representative Panel of Envelope Glycoproteins for Hepatitis C Virus Vaccine Development

Author

Salas, Jordan H., Urbanowicz, Richard A., Guest, Johnathan D., Frumento, Nicole, Figueroa, Alexis, Clark, Kaitlyn E., Keck, Zhenyong, Cowton, Vanessa M., Cole, Sarah J., Patel, Arvind H., Fuerst, Thomas R., Drummer, Heidi E., Major, Marian, Tarr, Alexander W., Ball, Jonathan K., Law, Mansun, Pierce, Brian G., Foung, Steven K.H., and Bailey, Justin R.

Published
2022
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5. Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer

Author

Guest, Johnathan D., Wang, Ruixue, Elkholy, Khadija H., Chagas, Andrezza, Chao, Kinlin L., Cleveland, Thomas E., Kim, Young Chang, Keck, Zhen-Yong, Marin, Alexander, Yunus, Abdul S., Mariuzza, Roy A., Andrianov, Alexander K., Toth, Eric A., Foung, Steven K. H., Pierce, Brian G., and Fuerst, Thomas R.

Published
2021

9. Impact of AlphaFold on structure prediction of protein complexes: The CASP15‐CAPRI experiment

Author

Lensink, Marc F., primary, Brysbaert, Guillaume, additional, Raouraoua, Nessim, additional, Bates, Paul A., additional, Giulini, Marco, additional, Honorato, Rodrigo V., additional, van Noort, Charlotte, additional, Teixeira, Joao M. C., additional, Bonvin, Alexandre M. J. J., additional, Kong, Ren, additional, Shi, Hang, additional, Lu, Xufeng, additional, Chang, Shan, additional, Liu, Jian, additional, Guo, Zhiye, additional, Chen, Xiao, additional, Morehead, Alex, additional, Roy, Raj S., additional, Wu, Tianqi, additional, Giri, Nabin, additional, Quadir, Farhan, additional, Chen, Chen, additional, Cheng, Jianlin, additional, Del Carpio, Carlos A., additional, Ichiishi, Eichiro, additional, Rodriguez‐Lumbreras, Luis A., additional, Fernandez‐Recio, Juan, additional, Harmalkar, Ameya, additional, Chu, Lee‐Shin, additional, Canner, Sam, additional, Smanta, Rituparna, additional, Gray, Jeffrey J., additional, Li, Hao, additional, Lin, Peicong, additional, He, Jiahua, additional, Tao, Huanyu, additional, Huang, Sheng‐You, additional, Roel‐Touris, Jorge, additional, Jimenez‐Garcia, Brian, additional, Christoffer, Charles W., additional, Jain, Anika J., additional, Kagaya, Yuki, additional, Kannan, Harini, additional, Nakamura, Tsukasa, additional, Terashi, Genki, additional, Verburgt, Jacob C., additional, Zhang, Yuanyuan, additional, Zhang, Zicong, additional, Fujuta, Hayato, additional, Sekijima, Masakazu, additional, Kihara, Daisuke, additional, Khan, Omeir, additional, Kotelnikov, Sergei, additional, Ghani, Usman, additional, Padhorny, Dzmitry, additional, Beglov, Dmitri, additional, Vajda, Sandor, additional, Kozakov, Dima, additional, Negi, Surendra S., additional, Ricciardelli, Tiziana, additional, Barradas‐Bautista, Didier, additional, Cao, Zhen, additional, Chawla, Mohit, additional, Cavallo, Luigi, additional, Oliva, Romina, additional, Yin, Rui, additional, Cheung, Melyssa, additional, Guest, Johnathan D., additional, Lee, Jessica, additional, Pierce, Brian G., additional, Shor, Ben, additional, Cohen, Tomer, additional, Halfon, Matan, additional, Schneidman‐Duhovny, Dina, additional, Zhu, Shaowen, additional, Yin, Rujie, additional, Sun, Yuanfei, additional, Shen, Yang, additional, Maszota‐Zieleniak, Martyna, additional, Bojarski, Krzysztof K., additional, Lubecka, Emilia A., additional, Marcisz, Mateusz, additional, Danielsson, Annemarie, additional, Dziadek, Lukasz, additional, Gaardlos, Margrethe, additional, Gieldon, Artur, additional, Liwo, Adam, additional, Samsonov, Sergey A., additional, Slusarz, Rafal, additional, Zieba, Karolina, additional, Sieradzan, Adam K., additional, Czaplewski, Cezary, additional, Kobayashi, Shinpei, additional, Miyakawa, Yuta, additional, Kiyota, Yasuomi, additional, Takeda‐Shitaka, Mayuko, additional, Olechnovic, Kliment, additional, Valancauskas, Lukas, additional, Dapkunas, Justas, additional, Venclovas, Ceslovas, additional, Wallner, Bjorn, additional, Yang, Lin, additional, Hou, Chengyu, additional, He, Xiaodong, additional, Guo, Shuai, additional, Jiang, Shenda, additional, Ma, Xiaoliang, additional, Duan, Rui, additional, Qui, Liming, additional, Xu, Xianjin, additional, Zou, Xiaoqin, additional, Velankar, Sameer, additional, and Wodak, Shoshana J., additional

Published
2023
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10. Molecular Characterization of AZD7442 (Tixagevimab-Cilgavimab) Neutralization of SARS-CoV-2 Omicron Subvariants

Author

Roe, Tiffany L., primary, Brady, Tyler, additional, Schuko, Nicolette, additional, Nguyen, Amy, additional, Beloor, Jagadish, additional, Guest, Johnathan D., additional, Aksyuk, Anastasia A., additional, Tuffy, Kevin M., additional, Zhang, Tianhui, additional, Streicher, Katie, additional, Kelly, Elizabeth J., additional, and Kijak, Gustavo H., additional

Published
2023
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11. Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

Author

Lensink, Marc F, Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A, Giulini, Marco, Honorato, Rodrigo V, van Noort, Charlotte, Teixeira, Joao M C, Bonvin, Alexandre M J J, Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S, Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A, Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A, Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J, Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W, Jain, Anika J, Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C, Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S, Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rujie, Cheung, Melyssa, Guest, Johnathan D, Lee, Jessica, Pierce, Brian G, Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K, Lubecka, Emilia A, Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A, Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K, Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Bjorn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, Wodak, Shoshana J, Lensink, Marc F, Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A, Giulini, Marco, Honorato, Rodrigo V, van Noort, Charlotte, Teixeira, Joao M C, Bonvin, Alexandre M J J, Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S, Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A, Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A, Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J, Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W, Jain, Anika J, Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C, Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S, Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rujie, Cheung, Melyssa, Guest, Johnathan D, Lee, Jessica, Pierce, Brian G, Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K, Lubecka, Emilia A, Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A, Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K, Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Bjorn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, and Wodak, Shoshana J

Abstract

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.

Published
2023

12. Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

Author

Sub NMR Spectroscopy, NMR Spectroscopy, Lensink, Marc F, Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A, Giulini, Marco, Honorato, Rodrigo V, van Noort, Charlotte, Teixeira, Joao M C, Bonvin, Alexandre M J J, Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S, Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A, Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A, Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J, Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W, Jain, Anika J, Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C, Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S, Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rujie, Cheung, Melyssa, Guest, Johnathan D, Lee, Jessica, Pierce, Brian G, Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K, Lubecka, Emilia A, Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A, Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K, Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Bjorn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, Wodak, Shoshana J, Sub NMR Spectroscopy, NMR Spectroscopy, Lensink, Marc F, Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A, Giulini, Marco, Honorato, Rodrigo V, van Noort, Charlotte, Teixeira, Joao M C, Bonvin, Alexandre M J J, Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S, Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A, Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A, Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J, Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W, Jain, Anika J, Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C, Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S, Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rujie, Cheung, Melyssa, Guest, Johnathan D, Lee, Jessica, Pierce, Brian G, Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K, Lubecka, Emilia A, Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A, Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K, Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Bjorn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, and Wodak, Shoshana J

Published
2023

13. Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

Author

Lensink, Marc F., Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A., Giulini, Marco, Honorato, Rodrigo V., van Noort, Charlotte, Teixeira, Joao M. C., Bonvin, Alexandre M. J. J., Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S., Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A., Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J., Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W., Jain, Anika J., Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C., Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S., Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rui, Cheung, Melyssa, Guest, Johnathan D., Lee, Jessica, Pierce, Brian G., Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Yin, Rujie, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K., Lubecka, Emilia A., Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A., Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K., Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Björn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, Wodak, Shoshana J., Lensink, Marc F., Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A., Giulini, Marco, Honorato, Rodrigo V., van Noort, Charlotte, Teixeira, Joao M. C., Bonvin, Alexandre M. J. J., Kong, Ren, Shi, Hang, Lu, Xufeng, Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S., Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A., Ichiishi, Eichiro, Rodriguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J., Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W., Jain, Anika J., Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C., Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S., Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rui, Cheung, Melyssa, Guest, Johnathan D., Lee, Jessica, Pierce, Brian G., Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Yin, Rujie, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K., Lubecka, Emilia A., Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Samsonov, Sergey A., Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K., Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Wallner, Björn, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Zou, Xiaoqin, Velankar, Sameer, and Wodak, Shoshana J.

Abstract

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem., Funding Agencies|Francis Crick Institute; Cancer Research UK [FC0001003]; UK Medical Research Council [FC001003]; Wellcome Trust [FC001003]; European Union Horizon 2020 [823830]; Netherlands e-Science Center [027.020.G13]; US National Institutes of Health [R01GM146340, R01GM093123]; Spanish Ministry of Science [501100011033, AEI/10.13039, PID2019-110167RB-I00]; National Institute of Health [R35 GM144083, RM1135136, R35GM118078, R01GM140098, R01GM123055, R01GM133840, R35-GM141881]; Advanced Research Computing at Hopkins (ARCH) core facility; National Natural Science Foundation of China [32161133002, 62072199]; European Molecular Biology Organization (EMBO) [ALTF 145-2021]; Government of Catalonia's Agency for Business Competitiveness (ACCIO); National Science Foundation [DMS 2054251, DBI2003635, IIS2211598, DBI2146026, MCB1925643, CMMI1825941, IIS1763246, DBI1759934, CCF-1943008, OAC1920103]; National Institute of General Medical Sciences [T32 GM132024]; NIH/NIGMS [R35GM136409, R35GM124952]; National Science Center of Poland (Narodowe Centrum Nauki) (NCN) [UMO2017/27/B/ST4/00926, UMO-2017/26/M/ ST4/00044, UMO2017/25/B/ST4/01026]; Research Council of Lithuania [: S-MIP-21-25]; Wallenberg AI, Autonomous System and Software Program (WASP); Knut and Alice Wallenberg Foundation (KAW); Swedish Research Council; Science Foundation of the National Key Laboratory of Science and Technology; Fundamental Research Funds for the Central Universities of China; [801342]

Published
2023
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14. Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

Author

Francis Crick Institute, Cancer Research UK, Medical Research Council (UK), Wellcome Trust, European Commission, National Science Foundation (US), National Institutes of Health (US), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Johns Hopkins University, National Natural Science Foundation of China, EMBO, Generalitat de Catalunya, Purdue University, National Science Centre (Poland), University of Warsaw, Research Council of Lithuania, Knut and Alice Wallenberg Foundation, Swedish Research Council, Lensink, Marc F., Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A., Giulini, Marco, Honorato, Rodrigo V., van Noort, Charlotte, Teixeira, Joao M. C., Bonvin, Alexandre M. J. J., Kong, Ren, Shi, Hang, Samsonov, Sergey A., Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K., Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Wallner, Bjorn, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Lu, Xufeng, Zou, Xiaoqin, Velankar, Sameer, Wodak, Shoshana J., Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S., Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A., Ichiishi, Eichiro, Rodríguez-Lumbreras, Luis A., Fernández-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J., Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W., Jain, Anika J., Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C., Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S., Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rui, Cheung, Melyssa, Guest, Johnathan D., Lee, Jessica, Pierce, Brian G., Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Yin, Rujie, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K., Lubecka, Emilia A., Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, Liwo, Adam, Francis Crick Institute, Cancer Research UK, Medical Research Council (UK), Wellcome Trust, European Commission, National Science Foundation (US), National Institutes of Health (US), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Johns Hopkins University, National Natural Science Foundation of China, EMBO, Generalitat de Catalunya, Purdue University, National Science Centre (Poland), University of Warsaw, Research Council of Lithuania, Knut and Alice Wallenberg Foundation, Swedish Research Council, Lensink, Marc F., Brysbaert, Guillaume, Raouraoua, Nessim, Bates, Paul A., Giulini, Marco, Honorato, Rodrigo V., van Noort, Charlotte, Teixeira, Joao M. C., Bonvin, Alexandre M. J. J., Kong, Ren, Shi, Hang, Samsonov, Sergey A., Slusarz, Rafal, Zieba, Karolina, Sieradzan, Adam K., Czaplewski, Cezary, Kobayashi, Shinpei, Miyakawa, Yuta, Kiyota, Yasuomi, Takeda-Shitaka, Mayuko, Olechnovic, Kliment, Wallner, Bjorn, Valancauskas, Lukas, Dapkunas, Justas, Venclovas, Ceslovas, Yang, Lin, Hou, Chengyu, He, Xiaodong, Guo, Shuai, Jiang, Shenda, Ma, Xiaoliang, Duan, Rui, Qui, Liming, Xu, Xianjin, Lu, Xufeng, Zou, Xiaoqin, Velankar, Sameer, Wodak, Shoshana J., Chang, Shan, Liu, Jian, Guo, Zhiye, Chen, Xiao, Morehead, Alex, Roy, Raj S., Wu, Tianqi, Giri, Nabin, Quadir, Farhan, Chen, Chen, Cheng, Jianlin, Del Carpio, Carlos A., Ichiishi, Eichiro, Rodríguez-Lumbreras, Luis A., Fernández-Recio, Juan, Harmalkar, Ameya, Chu, Lee-Shin, Canner, Sam, Smanta, Rituparna, Gray, Jeffrey J., Li, Hao, Lin, Peicong, He, Jiahua, Tao, Huanyu, Huang, Sheng-You, Roel-Touris, Jorge, Jimenez-Garcia, Brian, Christoffer, Charles W., Jain, Anika J., Kagaya, Yuki, Kannan, Harini, Nakamura, Tsukasa, Terashi, Genki, Verburgt, Jacob C., Zhang, Yuanyuan, Zhang, Zicong, Fujuta, Hayato, Sekijima, Masakazu, Kihara, Daisuke, Khan, Omeir, Kotelnikov, Sergei, Ghani, Usman, Padhorny, Dzmitry, Beglov, Dmitri, Vajda, Sandor, Kozakov, Dima, Negi, Surendra S., Ricciardelli, Tiziana, Barradas-Bautista, Didier, Cao, Zhen, Chawla, Mohit, Cavallo, Luigi, Oliva, Romina, Yin, Rui, Cheung, Melyssa, Guest, Johnathan D., Lee, Jessica, Pierce, Brian G., Shor, Ben, Cohen, Tomer, Halfon, Matan, Schneidman-Duhovny, Dina, Zhu, Shaowen, Yin, Rujie, Sun, Yuanfei, Shen, Yang, Maszota-Zieleniak, Martyna, Bojarski, Krzysztof K., Lubecka, Emilia A., Marcisz, Mateusz, Danielsson, Annemarie, Dziadek, Lukasz, Gaardlos, Margrethe, Gieldon, Artur, and Liwo, Adam

Abstract

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.

Published
2023

15. Structure-Based and Rational Design of a Hepatitis C Virus Vaccine

Author

Guest, Johnathan D., Guest, Johnathan D., Pierce, Brian G., Guest, Johnathan D., Guest, Johnathan D., and Pierce, Brian G.

Abstract

A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune evasion. Structure-based and rational vaccine design approaches have capitalized on insights regarding the immune response to HCV and the structures of antibody-bound envelope glycoproteins. Despite successes with other viruses, designing an immunogen based on HCV glycoproteins that can elicit broadly protective immunity against HCV infection is an ongoing challenge. Here, we describe HCV vaccine design approaches where immunogens were selected and optimized through analysis of available structures, identification of conserved epitopes targeted by neutralizing antibodies, or both. Several designs have elicited immune responses against HCV in vivo, revealing correlates of HCV antigen immunogenicity and breadth of induced responses. Recent studies have elucidated the functional, dynamic and immunological features of key regions of the viral envelope glycoproteins, which can inform next-generation immunogen design efforts. These insights and design strategies represent promising pathways to HCV vaccine development, which can be further informed by successful immunogen designs generated for other viruses.

Published
2021

16. Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate

Author

Wang, Ruixue, primary, Suzuki, Saori, additional, Guest, Johnathan D., additional, Heller, Brigitte, additional, Almeda, Maricar, additional, Andrianov, Alexander K., additional, Marin, Alexander, additional, Mariuzza, Roy A., additional, Keck, Zhen-Yong, additional, Foung, Steven K. H., additional, Yunus, Abdul S., additional, Pierce, Brian G., additional, Toth, Eric A., additional, Ploss, Alexander, additional, and Fuerst, Thomas R., additional

Published
2022
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17. An antigenically diverse, representative panel of envelope glycoproteins for HCV vaccine development

Author

Salas, Jordan H., Urbanowicz, Richard A., Guest, Johnathan D., Frumento, Nicole, Figueroa, Alexis, Clark, Kaitlyn E., Keck, Zhenyong, Cowton, Vanessa M., Cole, Sarah J., Patel, Arvind H., Fuerst, Thomas R., Drummer, Heidi E., Major, Marian, Tarr, Alexander W., Ball, Jonathan K., Law, Mansun, Pierce, Brian G., Foung, Steven K.H., and Bailey, Justin R.

Abstract

Background and Aims:\ud \ud Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpp) for neutralization assays.\ud \ud Methods:\ud \ud We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpp. Neutralization sensitivity of these HCVpp varied widely. HCVpp clustered into 15 distinct groups based on patterns of relative sensitivity to seven broadly neutralizing monoclonal antibodies (bNAbs). We used these data to select a final panel of 15 antigenically representative HCVpp.\ud \ud Results:\ud \ud Both the 65 and 15 HCVpp panels span four tiers of neutralization sensitivity, and neutralizing breadth measurements for seven bNAbs were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpp were independent of genetic distances between E1E2 clones.\ud \ud Conclusions:\ud \ud Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity, rather than panels selected solely for genetic diversity. We propose that this multi-tier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.

Published
2021

18. Prediction of protein assemblies, the next frontier: The CASP14‐CAPRI experiment

Author

Lensink, Marc F., primary, Brysbaert, Guillaume, additional, Mauri, Théo, additional, Nadzirin, Nurul, additional, Velankar, Sameer, additional, Chaleil, Raphael A. G., additional, Clarence, Tereza, additional, Bates, Paul A., additional, Kong, Ren, additional, Liu, Bin, additional, Yang, Guangbo, additional, Liu, Ming, additional, Shi, Hang, additional, Lu, Xufeng, additional, Chang, Shan, additional, Roy, Raj S., additional, Quadir, Farhan, additional, Liu, Jian, additional, Cheng, Jianlin, additional, Antoniak, Anna, additional, Czaplewski, Cezary, additional, Giełdoń, Artur, additional, Kogut, Mateusz, additional, Lipska, Agnieszka G., additional, Liwo, Adam, additional, Lubecka, Emilia A., additional, Maszota‐Zieleniak, Martyna, additional, Sieradzan, Adam K., additional, Ślusarz, Rafał, additional, Wesołowski, Patryk A., additional, Zięba, Karolina, additional, Del Carpio Muñoz, Carlos A., additional, Ichiishi, Eiichiro, additional, Harmalkar, Ameya, additional, Gray, Jeffrey J., additional, Bonvin, Alexandre M. J. J., additional, Ambrosetti, Francesco, additional, Vargas Honorato, Rodrigo, additional, Jandova, Zuzana, additional, Jiménez‐García, Brian, additional, Koukos, Panagiotis I., additional, Van Keulen, Siri, additional, Van Noort, Charlotte W., additional, Réau, Manon, additional, Roel‐Touris, Jorge, additional, Kotelnikov, Sergei, additional, Padhorny, Dzmitry, additional, Porter, Kathryn A., additional, Alekseenko, Andrey, additional, Ignatov, Mikhail, additional, Desta, Israel, additional, Ashizawa, Ryota, additional, Sun, Zhuyezi, additional, Ghani, Usman, additional, Hashemi, Nasser, additional, Vajda, Sandor, additional, Kozakov, Dima, additional, Rosell, Mireia, additional, Rodríguez‐Lumbreras, Luis A., additional, Fernandez‐Recio, Juan, additional, Karczynska, Agnieszka, additional, Grudinin, Sergei, additional, Yan, Yumeng, additional, Li, Hao, additional, Lin, Peicong, additional, Huang, Sheng‐You, additional, Christoffer, Charles, additional, Terashi, Genki, additional, Verburgt, Jacob, additional, Sarkar, Daipayan, additional, Aderinwale, Tunde, additional, Wang, Xiao, additional, Kihara, Daisuke, additional, Nakamura, Tsukasa, additional, Hanazono, Yuya, additional, Gowthaman, Ragul, additional, Guest, Johnathan D., additional, Yin, Rui, additional, Taherzadeh, Ghazaleh, additional, Pierce, Brian G., additional, Barradas‐Bautista, Didier, additional, Cao, Zhen, additional, Cavallo, Luigi, additional, Oliva, Romina, additional, Sun, Yuanfei, additional, Zhu, Shaowen, additional, Shen, Yang, additional, Park, Taeyong, additional, Woo, Hyeonuk, additional, Yang, Jinsol, additional, Kwon, Sohee, additional, Won, Jonghun, additional, Seok, Chaok, additional, Kiyota, Yasuomi, additional, Kobayashi, Shinpei, additional, Harada, Yoshiki, additional, Takeda‐Shitaka, Mayuko, additional, Kundrotas, Petras J., additional, Singh, Amar, additional, Vakser, Ilya A., additional, Dapkūnas, Justas, additional, Olechnovič, Kliment, additional, Venclovas, Česlovas, additional, Duan, Rui, additional, Qiu, Liming, additional, Xu, Xianjin, additional, Zhang, Shuang, additional, Zou, Xiaoqin, additional, and Wodak, Shoshana J., additional

Published
2021
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21. Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

Author

Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphael A.G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Shan, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdoń, Artur, Kogut, Mateusz, Lipska, Agnieszka G., Liwo, Adam, Lubecka, Emilia A., Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Del Carpio Muñoz, Carlos A., Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M.J.J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Van Keulen, Siri, Van Noort, Charlotte W., Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergei, Padhorny, Dzmitry, Porter, Kathryn A., Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Yuya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkūnas, Justas, Olechnovič, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, Wodak, Shoshana J., Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphael A.G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Shan, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdoń, Artur, Kogut, Mateusz, Lipska, Agnieszka G., Liwo, Adam, Lubecka, Emilia A., Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Del Carpio Muñoz, Carlos A., Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M.J.J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Van Keulen, Siri, Van Noort, Charlotte W., Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergei, Padhorny, Dzmitry, Porter, Kathryn A., Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Yuya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkūnas, Justas, Olechnovič, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, and Wodak, Shoshana J.

Abstract

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.

Published
2021

22. Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

Author

Sub NMR Spectroscopy, Sub Overig UiLOTS, Sub Mathematics Education, NMR Spectroscopy, Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphael A.G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Shan, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdoń, Artur, Kogut, Mateusz, Lipska, Agnieszka G., Liwo, Adam, Lubecka, Emilia A., Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Del Carpio Muñoz, Carlos A., Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M.J.J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Van Keulen, Siri, Van Noort, Charlotte W., Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergei, Padhorny, Dzmitry, Porter, Kathryn A., Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Yuya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkūnas, Justas, Olechnovič, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, Wodak, Shoshana J., Sub NMR Spectroscopy, Sub Overig UiLOTS, Sub Mathematics Education, NMR Spectroscopy, Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphael A.G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Shan, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdoń, Artur, Kogut, Mateusz, Lipska, Agnieszka G., Liwo, Adam, Lubecka, Emilia A., Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Del Carpio Muñoz, Carlos A., Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M.J.J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Van Keulen, Siri, Van Noort, Charlotte W., Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergei, Padhorny, Dzmitry, Porter, Kathryn A., Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernandez-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Yuya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkūnas, Justas, Olechnovič, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, and Wodak, Shoshana J.

Published
2021

23. Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

Author

Cancer Research UK, Department of Energy and Climate Change (UK), European Commission, Institut National de Recherche en Informatique et en Automatique (France), Medical Research Council (UK), Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Institute of General Medical Sciences (US), National Institutes of Health (US), National Natural Science Foundation of China, National Science Foundation (US), Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphaël A. G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Xang, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdón, Artur, Kogut, Mateusz, Lipska, Agnieszka, Liwo, Adam, Lubecka, Emilia, Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Carpio Muñoz, Carlos A. del, Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M. J. J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Keulen, Siri van, Noort, Charlotte W. van, Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergey, Padhorny, Dzmitry, Porter, Kathryn, Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernández-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng-You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Huya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkunas, Justas, Olechnovic, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, Wodak, Shoshana J., Cancer Research UK, Department of Energy and Climate Change (UK), European Commission, Institut National de Recherche en Informatique et en Automatique (France), Medical Research Council (UK), Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Institute of General Medical Sciences (US), National Institutes of Health (US), National Natural Science Foundation of China, National Science Foundation (US), Lensink, Marc F., Brysbaert, Guillaume, Mauri, Théo, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphaël A. G., Clarence, Tereza, Bates, Paul A., Kong, Ren, Liu, Bin, Yang, Guangbo, Liu, Ming, Shi, Hang, Lu, Xufeng, Chang, Xang, Roy, Raj S., Quadir, Farhan, Liu, Jian, Cheng, Jianlin, Antoniak, Anna, Czaplewski, Cezary, Giełdón, Artur, Kogut, Mateusz, Lipska, Agnieszka, Liwo, Adam, Lubecka, Emilia, Maszota-Zieleniak, Martyna, Sieradzan, Adam K., Ślusarz, Rafał, Wesołowski, Patryk A., Zięba, Karolina, Carpio Muñoz, Carlos A. del, Ichiishi, Eiichiro, Harmalkar, Ameya, Gray, Jeffrey J., Bonvin, Alexandre M. J. J., Ambrosetti, Francesco, Vargas Honorato, Rodrigo, Jandova, Zuzana, Jiménez-García, Brian, Koukos, Panagiotis I., Keulen, Siri van, Noort, Charlotte W. van, Réau, Manon, Roel-Touris, Jorge, Kotelnikov, Sergey, Padhorny, Dzmitry, Porter, Kathryn, Alekseenko, Andrey, Ignatov, Mikhail, Desta, Israel, Ashizawa, Ryota, Sun, Zhuyezi, Ghani, Usman, Hashemi, Nasser, Vajda, Sandor, Kozakov, Dima, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Fernández-Recio, Juan, Karczynska, Agnieszka, Grudinin, Sergei, Yan, Yumeng, Li, Hao, Lin, Peicong, Huang, Sheng-You, Christoffer, Charles, Terashi, Genki, Verburgt, Jacob, Sarkar, Daipayan, Aderinwale, Tunde, Wang, Xiao, Kihara, Daisuke, Nakamura, Tsukasa, Hanazono, Huya, Gowthaman, Ragul, Guest, Johnathan D., Yin, Rui, Taherzadeh, Ghazaleh, Pierce, Brian G., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Sun, Yuanfei, Zhu, Shaowen, Shen, Yang, Park, Taeyong, Woo, Hyeonuk, Yang, Jinsol, Kwon, Sohee, Won, Jonghun, Seok, Chaok, Kiyota, Yasuomi, Kobayashi, Shinpei, Harada, Yoshiki, Takeda-Shitaka, Mayuko, Kundrotas, Petras J., Singh, Amar, Vakser, Ilya A., Dapkunas, Justas, Olechnovic, Kliment, Venclovas, Česlovas, Duan, Rui, Qiu, Liming, Xu, Xianjin, Zhang, Shuang, Zou, Xiaoqin, and Wodak, Shoshana J.

Abstract

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.

Published
2021

25. CoV3D: A database of high resolution coronavirus protein structures

Author

Gowthaman, Ragul, Guest, Johnathan D, Yin, Rui, and Pierce, Brian G

Subjects
viruses
Abstract

Coronaviruses represent a major global threat as emerging pathogens, most recently SARS-CoV-2, the etiologic agent behind COVID-19, which is currently causing a global pandemic. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal critical targets on the virus and a map of vulnerabilities. To enable structure-based design of vaccines and therapeutics, as well as insights into structural and molecular features of coronaviruses, we have developed the CoV3D database, which provides a view of SARS-CoV-2 and other coronavirus protein structures, updated on a weekly basis. This database includes and annotates structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Additionally, CoV3D provides information on spike glycoprotein sequence variability and polymorphisms, mapping these features onto the spike structure, and includes spike structures with modeled glycosylation. CoV3D is available at: https://cov3d.ibbr.umd.edu.

Published
2020
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27. Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization

Author

Pierce, Brian G., primary, Keck, Zhen-Yong, additional, Wang, Ruixue, additional, Lau, Patrick, additional, Garagusi, Kyle, additional, Elkholy, Khadija, additional, Toth, Eric A., additional, Urbanowicz, Richard A., additional, Guest, Johnathan D., additional, Agnihotri, Pragati, additional, Kerzic, Melissa C., additional, Marin, Alexander, additional, Andrianov, Alexander K., additional, Ball, Jonathan K., additional, Mariuzza, Roy A., additional, Fuerst, Thomas R., additional, and Foung, Steven K. H., additional

Published
2020
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31. Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate.

Author

Ruixue Wang, Suzuki, Saori, Guest, Johnathan D., Heller, Brigitte, Almeda, Maricar, Andrianov, Alexander K., Marin, Alexander, Mariuzza, Roy A., Zhen-Yong Keck, Foung, Steven K. H., Yunus, Abdul S., Pierce, Brian G., Toth, Eric A., Ploss, Alexander, and Fuerst, Thomas R.

Subjects
HEPATITIS C virus, HETERODIMERS, CHRONIC hepatitis C, IMMUNOGLOBULINS, GLOBAL burden of disease
Abstract

Hepatitis C virus (HCV) is a global disease burden, and a preventive vaccine is needed to control or eradicate the virus. Despite the advent of effective antiviral therapy, this treatment is not accessible to many patients and does not prevent reinfection, making chronic hepatitis C an ongoing global health problem. Thus, development of a prophylactic vaccine will represent a significant step toward global eradication of HCV. HCV exhibits high genetic variability, which leads frequently to immune escape. However, a considerable challenge faced in HCV vaccine development is designing an antigen that elicits broadly neutralizing antibodies. Here, we characterized the immunogenicity of a vaccine based on a soluble, secreted form of the E1E2 envelope heterodimer (sE1E2.LZ). Sera from mice immunized with sE1E2.LZ exhibited an anti-E1E2-specific response comparable to mice immunized with membrane-bound E1E2 (mbE1E2) or a soluble E2 ectodomain (sE2). In competition-inhibition ELISA using antigenic domain-specific neutralizing and nonneutralizing antibodies, sera from sE1E2.LZ-immunized mice showed nearly identical or stronger competition toward neutralizing antibodies when compared with mbE1E2. In contrast, sera from mice immunized with sE2, and to a lesser extent mbE1E2, competed more effectively with nonneutralizing antibodies. An assessment of neutralization activity using both HCV pseudoparticles and cell culture-derived infectious HCV showed that immunization with sE1E2.LZ elicited the broadest neutralization activity of the three antigens, and sE1E2.LZ induced neutralization activity against all genotypes. These results indicate that our native-like soluble glycoprotein design, sE1E2.LZ, induces broadly neutralizing antibodies and serves as a promising vaccine candidate for further development. [ABSTRACT FROM AUTHOR]

Published
2022
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32. Broadly neutralizing antibodies from an individual that naturally cleared multiple hepatitis c virus infections uncover molecular determinants for E2 targeting and vaccine design

Author

Keck, Zhen Yong, Pierce, Brian G., Lau, Patrick, Lu, Janine, Wang, Yong, Underwood, Alexander, Bull, Rowena A., Prentoe, Jannick, Velázquez-Moctezuma, Rodrigo, Walker, Melanie R., Luciani, Fabio, Guest, Johnathan D., Fauvelle, Catherine, Baumert, Thomas F., Bukh, Jens, Lloyd, Andrew R., Foung, Steven K.H., Keck, Zhen Yong, Pierce, Brian G., Lau, Patrick, Lu, Janine, Wang, Yong, Underwood, Alexander, Bull, Rowena A., Prentoe, Jannick, Velázquez-Moctezuma, Rodrigo, Walker, Melanie R., Luciani, Fabio, Guest, Johnathan D., Fauvelle, Catherine, Baumert, Thomas F., Bukh, Jens, Lloyd, Andrew R., and Foung, Steven K.H.

Abstract

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine.

Published
2019

33. Blind prediction of homo- and hetero-protein complexes: The CASP13-CAPRI experiment

Author

Agence Nationale de la Recherche (France), Cancer Research UK, European Commission, Medical Research Council (UK), National Institutes of Health (US), National Natural Science Foundation of China, National Research Foundation of Korea, National Science Foundation (US), Ministerio de Economía y Competitividad (España), Università degli Studi di Napoli PARTHENOPE, Wellcome Trust, Lensink, Marc F., Brysbaert, Guillaume, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphaël A. G., Gerguri, Tereza, Bates, Paul A., Laine, Elodie, Carbone, Alessandra, Grudinin, Sergei, Kong, Ren, Weng, Zhiping, Guest, Johnathan D., Gowthaman, Ragul, Pierce, Brian G., Xu, Xianjin, Duan, Rui, Qiu, Liming, Hou, Jie, Merideth, Benjamin Ryan, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Koukos, Panagiotis I., Roel-Touris, Jorge, Ambrosetti, Francesco, Geng, Cunliang, Schaarschmidt, Jörg, Trellet, Mikael E., Melquiond, Adrien S. J., Xue, Li, Jiménez-García, Brian, Noort, Charlotte W. van, Honorato, Rodrigo V., Bonvin, A. M. J. J., Wodak, Shoshana J., Liu, Ran-Ran, Xu, Xi-Ming, Shi, Hang, Chang, Shan, Eisenstein, Miriam, Karczynska, Agnieszka, Czaplewski, Cezary, Emilia Lubecka, Emilia, Lipska, Agnieszka, Krupa, Paweł, Mozolewska, Magdalena, Golon, Łukasz, Samsonov, Sergey, Liwo, Adam, Crivelli, Silvia, Pagès, Guillaume, Karasikov, Mikhaill, Kadukova, Maria, Yan, Yumeng, Huang, Sheng-You, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Romero-Durana, Miguel, Díaz-Bueno, Lucía, Fernández-Recio, Juan, Christoffer, Charles, Terashi, Genki, Shin, Woong-Hee, Aderinwale, Tunde, Venkata Subraman, Sai Raghavendra Maddhuri, Kihara, Daisuke, Kozakov, Dima, Vajda, Sandor, Porter, Kathryn, Padhorny, Dzmitry, Desta, Israel, Beglov, Dmitri, Ignatov, Mikhail, Kotelnikov, Sergey, Moal, Iain H., Ritchie, David W., Chauvot de Beauchêne, Isaure, Maigret, Bernard, Devignes, Marie-Dominique, Ruiz Echartea, Maria E., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Cao, Yue, Shen, Yang, Baek, Minkyung, Park, Taeyong, Woo, Hyeonuk, Seok, Chaok, Braitbard, Merav, Bitton, Lirane, Scheidman-Duhovny, Dina, Dapkunas, Justas, Olechnovic, Kliment, Venclovas, Česlovas, Kundrotas, Petras J., Belkin, Saveliy, Chakravarty, Devlina, Badal, Varsha D., Vakser, Ilya A., Vreven, Thom, Vangaveti, Sweta, Borrman, Tyler, Agence Nationale de la Recherche (France), Cancer Research UK, European Commission, Medical Research Council (UK), National Institutes of Health (US), National Natural Science Foundation of China, National Research Foundation of Korea, National Science Foundation (US), Ministerio de Economía y Competitividad (España), Università degli Studi di Napoli PARTHENOPE, Wellcome Trust, Lensink, Marc F., Brysbaert, Guillaume, Nadzirin, Nurul, Velankar, Sameer, Chaleil, Raphaël A. G., Gerguri, Tereza, Bates, Paul A., Laine, Elodie, Carbone, Alessandra, Grudinin, Sergei, Kong, Ren, Weng, Zhiping, Guest, Johnathan D., Gowthaman, Ragul, Pierce, Brian G., Xu, Xianjin, Duan, Rui, Qiu, Liming, Hou, Jie, Merideth, Benjamin Ryan, Ma, Zhiwei, Cheng, Jianlin, Zou, Xiaoqin, Koukos, Panagiotis I., Roel-Touris, Jorge, Ambrosetti, Francesco, Geng, Cunliang, Schaarschmidt, Jörg, Trellet, Mikael E., Melquiond, Adrien S. J., Xue, Li, Jiménez-García, Brian, Noort, Charlotte W. van, Honorato, Rodrigo V., Bonvin, A. M. J. J., Wodak, Shoshana J., Liu, Ran-Ran, Xu, Xi-Ming, Shi, Hang, Chang, Shan, Eisenstein, Miriam, Karczynska, Agnieszka, Czaplewski, Cezary, Emilia Lubecka, Emilia, Lipska, Agnieszka, Krupa, Paweł, Mozolewska, Magdalena, Golon, Łukasz, Samsonov, Sergey, Liwo, Adam, Crivelli, Silvia, Pagès, Guillaume, Karasikov, Mikhaill, Kadukova, Maria, Yan, Yumeng, Huang, Sheng-You, Rosell, Mireia, Rodríguez-Lumbreras, Luis A., Romero-Durana, Miguel, Díaz-Bueno, Lucía, Fernández-Recio, Juan, Christoffer, Charles, Terashi, Genki, Shin, Woong-Hee, Aderinwale, Tunde, Venkata Subraman, Sai Raghavendra Maddhuri, Kihara, Daisuke, Kozakov, Dima, Vajda, Sandor, Porter, Kathryn, Padhorny, Dzmitry, Desta, Israel, Beglov, Dmitri, Ignatov, Mikhail, Kotelnikov, Sergey, Moal, Iain H., Ritchie, David W., Chauvot de Beauchêne, Isaure, Maigret, Bernard, Devignes, Marie-Dominique, Ruiz Echartea, Maria E., Barradas-Bautista, Didier, Cao, Zhen, Cavallo, Luigi, Oliva, Romina, Cao, Yue, Shen, Yang, Baek, Minkyung, Park, Taeyong, Woo, Hyeonuk, Seok, Chaok, Braitbard, Merav, Bitton, Lirane, Scheidman-Duhovny, Dina, Dapkunas, Justas, Olechnovic, Kliment, Venclovas, Česlovas, Kundrotas, Petras J., Belkin, Saveliy, Chakravarty, Devlina, Badal, Varsha D., Vakser, Ilya A., Vreven, Thom, Vangaveti, Sweta, and Borrman, Tyler

Abstract

We present the results for CAPRI Round 46, the third joint CASP‐CAPRI protein assembly prediction challenge. The Round comprised a total of 20 targets including 14 homo‐oligomers and 6 heterocomplexes. Eight of the homo‐oligomer targets and one heterodimer comprised proteins that could be readily modeled using templates from the Protein Data Bank, often available for the full assembly. The remaining 11 targets comprised 5 homodimers, 3 heterodimers, and two higher‐order assemblies. These were more difficult to model, as their prediction mainly involved “ab‐initio” docking of subunit models derived from distantly related templates. A total of ~30 CAPRI groups, including 9 automatic servers, submitted on average ~2000 models per target. About 17 groups participated in the CAPRI scoring rounds, offered for most targets, submitting ~170 models per target. The prediction performance, measured by the fraction of models of acceptable quality or higher submitted across all predictors groups, was very good to excellent for the nine easy targets. Poorer performance was achieved by predictors for the 11 difficult targets, with medium and high quality models submitted for only 3 of these targets. A similar performance “gap” was displayed by scorer groups, highlighting yet again the unmet challenge of modeling the conformational changes of the protein components that occur upon binding or that must be accounted for in template‐based modeling. Our analysis also indicates that residues in binding interfaces were less well predicted in this set of targets than in previous Rounds, providing useful insights for directions of future improvements.

Published
2019

34. Blind prediction of homo‐ and hetero‐protein complexes: The CASP13‐CAPRI experiment

Author

Lensink, Marc F., primary, Brysbaert, Guillaume, additional, Nadzirin, Nurul, additional, Velankar, Sameer, additional, Chaleil, Raphaël A. G., additional, Gerguri, Tereza, additional, Bates, Paul A., additional, Laine, Elodie, additional, Carbone, Alessandra, additional, Grudinin, Sergei, additional, Kong, Ren, additional, Liu, Ran‐Ran, additional, Xu, Xi‐Ming, additional, Shi, Hang, additional, Chang, Shan, additional, Eisenstein, Miriam, additional, Karczynska, Agnieszka, additional, Czaplewski, Cezary, additional, Lubecka, Emilia, additional, Lipska, Agnieszka, additional, Krupa, Paweł, additional, Mozolewska, Magdalena, additional, Golon, Łukasz, additional, Samsonov, Sergey, additional, Liwo, Adam, additional, Crivelli, Silvia, additional, Pagès, Guillaume, additional, Karasikov, Mikhail, additional, Kadukova, Maria, additional, Yan, Yumeng, additional, Huang, Sheng‐You, additional, Rosell, Mireia, additional, Rodríguez‐Lumbreras, Luis A., additional, Romero‐Durana, Miguel, additional, Díaz‐Bueno, Lucía, additional, Fernandez‐Recio, Juan, additional, Christoffer, Charles, additional, Terashi, Genki, additional, Shin, Woong‐Hee, additional, Aderinwale, Tunde, additional, Maddhuri Venkata Subraman, Sai Raghavendra, additional, Kihara, Daisuke, additional, Kozakov, Dima, additional, Vajda, Sandor, additional, Porter, Kathryn, additional, Padhorny, Dzmitry, additional, Desta, Israel, additional, Beglov, Dmitri, additional, Ignatov, Mikhail, additional, Kotelnikov, Sergey, additional, Moal, Iain H., additional, Ritchie, David W., additional, Chauvot de Beauchêne, Isaure, additional, Maigret, Bernard, additional, Devignes, Marie‐Dominique, additional, Ruiz Echartea, Maria E., additional, Barradas‐Bautista, Didier, additional, Cao, Zhen, additional, Cavallo, Luigi, additional, Oliva, Romina, additional, Cao, Yue, additional, Shen, Yang, additional, Baek, Minkyung, additional, Park, Taeyong, additional, Woo, Hyeonuk, additional, Seok, Chaok, additional, Braitbard, Merav, additional, Bitton, Lirane, additional, Scheidman‐Duhovny, Dina, additional, Dapkūnas, Justas, additional, Olechnovič, Kliment, additional, Venclovas, Česlovas, additional, Kundrotas, Petras J., additional, Belkin, Saveliy, additional, Chakravarty, Devlina, additional, Badal, Varsha D., additional, Vakser, Ilya A., additional, Vreven, Thom, additional, Vangaveti, Sweta, additional, Borrman, Tyler, additional, Weng, Zhiping, additional, Guest, Johnathan D., additional, Gowthaman, Ragul, additional, Pierce, Brian G., additional, Xu, Xianjin, additional, Duan, Rui, additional, Qiu, Liming, additional, Hou, Jie, additional, Ryan Merideth, Benjamin, additional, Ma, Zhiwei, additional, Cheng, Jianlin, additional, Zou, Xiaoqin, additional, Koukos, Panagiotis I., additional, Roel‐Touris, Jorge, additional, Ambrosetti, Francesco, additional, Geng, Cunliang, additional, Schaarschmidt, Jörg, additional, Trellet, Mikael E., additional, Melquiond, Adrien S. J., additional, Xue, Li, additional, Jiménez‐García, Brian, additional, van Noort, Charlotte W., additional, Honorato, Rodrigo V., additional, Bonvin, Alexandre M. J. J., additional, and Wodak, Shoshana J., additional

Published
2019
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35. Broadly neutralizing antibodies from an individual that naturally cleared multiple hepatitis C virus infections uncover molecular determinants for E2 targeting and vaccine design

Author

Keck, Zhen-Yong, primary, Pierce, Brian G., additional, Lau, Patrick, additional, Lu, Janine, additional, Wang, Yong, additional, Underwood, Alexander, additional, Bull, Rowena A., additional, Prentoe, Jannick, additional, Velázquez-Moctezuma, Rodrigo, additional, Walker, Melanie R., additional, Luciani, Fabio, additional, Guest, Johnathan D., additional, Fauvelle, Catherine, additional, Baumert, Thomas F., additional, Bukh, Jens, additional, Lloyd, Andrew R., additional, and Foung, Steven K. H., additional

Published
2019
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36. Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells

Author

Urbanowicz, Richard A., primary, Wang, Ruixue, additional, Schiel, John E., additional, Keck, Zhen-yong, additional, Kerzic, Melissa C., additional, Lau, Patrick, additional, Rangarajan, Sneha, additional, Garagusi, Kyle J., additional, Tan, Lei, additional, Guest, Johnathan D., additional, Ball, Jonathan K., additional, Pierce, Brian G., additional, Mariuzza, Roy A., additional, Foung, Steven K. H., additional, and Fuerst, Thomas R., additional

Published
2019
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39. Antigenicity and Immunogenicity of Differentially Glycosylated HCV E2 Envelope Proteins Expressed in Mammalian and Insect Cells.

Author

Urbanowicz, Richard A., Ruixue Wang, Schiel, John E., Zhen-yong Keck, Kerzic, Melissa C., Lau, Patrick, Rangarajan, Sneha, Garagusi, Kyle J., Tan, Lei, Guest, Johnathan D., Ball, Jonathan K., Pierce, Brian G., Mariuzza, Roy A., Foung, Steven K. H., and Fuerst, Thomas R.

Subjects
*VIRAL envelope proteins, *ANTIBODY formation, *HEPATITIS C virus, *PROTEINS, *INSECTS, *CARRIER proteins
Abstract

Development of a prophylactic vaccine for hepatitis C virus (HCV) remains a global health challenge. Cumulative evidence supports the importance of antibodies targeting the HCV E2 envelope glycoprotein to facilitate viral clearance. However, a significant challenge for a B cell-based vaccine is focusing the immune response on conserved E2 epitopes capable of eliciting neutralizing antibodies not associated with viral escape. We hypothesized that glycosylation might influence the antigenicity and immunogenicity of E2. Accordingly, we performed head-to-head molecular, antigenic and immunogenic comparisons of soluble E2 (sE2) produced in (i) mammalian (HEK293) cells, which confer mostly complex and high mannose type glycans; and (ii) insect (Sf9) cells, which impart mainly paucimannose type glycans. Mass spectrometry demonstrated that all 11 predicted N-glycosylation sites were utilized in both HEK293- and Sf9-derived sE2, but that N-glycans in insect sE2 were on average smaller and less complex. Both proteins bound CD81 and were recognized by conformation-dependent antibodies. Mouse immunogenicity studies revealed that similar polyclonal antibody responses were generated against antigenic domains A-E of E2. Although neutralizing antibody titers showed that Sf9-derived sE2 induced moderately stronger responses than HEK293-derived sE2 against the homologous HCV H77c isolate, the two proteins elicited comparable neutralization titers against heterologous isolates. Given that global alteration of HCV E2 glycosylation by expression in different hosts did not appreciably affect antigenicity or overall immunogenicity, a more productive approach to increasing the antibody response to neutralizing epitopes may be complete deletion, rather than just modification, of specific N-glycans proximal to these epitopes. [ABSTRACT FROM AUTHOR]

Published
2019
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40. A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.

Author

Sajadi MM, Abbasi A, Tehrani ZR, Siska C, Clark R, Chi W, Seaman MS, Mielke D, Wagh K, Liu Q, Jumpa T, Ketchem RR, Nguyen DN, Tolbert WD, Pierce BG, Atkinson B, Deming D, Sprague M, Asakawa A, Ferrer D, Dunn Y, Calvillo S, Yin R, Guest JD, Korber B, Mayer BT, Sato AH, Ouyang X, Foulke S, Habibzadeh P, Karimi M, Aslanabadi A, Hojabri M, Saadat S, Zareidoodeji R, Kędzior M, Pozharski E, Heredia A, Montefiori D, Ferrari G, Pazgier M, Lewis GK, Jardine JG, Lusso P, and DeVico A

Abstract

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.3, purified from the plasma of an HIV elite-neutralizer. Through a series of rational modifications we produced a variant that demonstrates: enhanced potency; superior antiviral activity in combination with other bnAbs; low polyreactivity; and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

Published
2024
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