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Your search keyword '"Musiani, Francesco"' showing total 20 results
Start Over Author "Musiani, Francesco" Publisher american chemical society (acs)
20 results on '"Musiani, Francesco"'

1. A community effort to discover small molecule SARS-CoV-2 inhibitors

Author

Schimunek, Johannes, primary, Seidl, Philipp, additional, Elez, Katarina, additional, Hempel, Tim, additional, Le, Tuan, additional, Noé, Frank, additional, Olsson, Simon, additional, Raich, Lluís, additional, Winter, Robin, additional, Gokcan, Hatice, additional, Gusev, Filipp, additional, Gutkin, Evgeny M., additional, Isayev, Olexandr, additional, Kurnikova, Maria G., additional, Narangoda, Chamali H., additional, Zubatyuk, Roman, additional, Bosko, Ivan P., additional, Furs, Konstantin V., additional, Karpenko, Anna D., additional, Kornoushenko, Yury V., additional, Shuldau, Mikita, additional, Yushkevich, Artsemi, additional, Benabderrahmane, Mohammed B., additional, Bousquet-Melou, Patrick, additional, Bureau, Ronan, additional, Charton, Beatrice, additional, Cirou, Bertrand C., additional, Gil, Gérard, additional, Allen, William J., additional, Sirimulla, Suman, additional, Watowich, Stanley, additional, Antonopoulos, Nick A., additional, Epitropakis, Nikolaos E., additional, Krasoulis, Agamemnon K., additional, Pitsikalis, Vassilis P., additional, Theodorakis, Stavros T., additional, Kozlovskii, Igor, additional, Maliutin, Anton, additional, Medvedev, Alexander, additional, Popov, Petr, additional, Zaretckii, Mark, additional, Eghbal-zadeh, Hamid, additional, Halmich, Christina, additional, Hochreiter, Sepp, additional, Mayr, Andreas, additional, Ruch, Peter, additional, Widrich, Michael, additional, Berenger, Francois, additional, Kumar, Ashutosh, additional, Yamanishi, Yoshihiro, additional, Zhang, Kam Y.J., additional, Bengio, Emmanuel, additional, Bengio, Yoshua, additional, Jain, Moksh J., additional, Korablyov, Maksym, additional, Liu, Cheng-Hao, additional, Marcou, Gilles, additional, Glaab, Enrico, additional, Barnsley, Kelly, additional, Iyengar, Suhasini M., additional, Ondrechen, Mary Jo, additional, Haupt, V. Joachim, additional, Kaiser, Florian, additional, Schroeder, Michael, additional, Pugliese, Luisa, additional, Albani, Simone, additional, Athanasiou, Christina, additional, Beccari, Andrea, additional, Carloni, Paolo, additional, D'Arrigo, Giulia, additional, Gianquinto, Eleonora, additional, Goßen, Jonas, additional, Hanke, Anton, additional, Joseph, Benjamin P., additional, Kokh, Daria B., additional, Kovachka, Sandra, additional, Manelfi, Candida, additional, Mukherjee, Goutam, additional, Muñiz-Chicharro, Abraham, additional, Musiani, Francesco, additional, Nunes-Alves, Ariane, additional, Paiardi, Giulia, additional, Rossetti, Giulia, additional, Sadiq, S. Kashif, additional, Spyrakis, Francesca, additional, Talarico, Carmine, additional, Tsengenes, Alexandros, additional, Wade, Rebecca C., additional, Copeland, Conner, additional, Gaiser, Jeremiah, additional, Olson, Daniel R., additional, Roy, Amitava, additional, Venkatraman, Vishwesh, additional, Wheeler, Travis J., additional, Arthanari, Haribabu, additional, Blaschitz, Klara, additional, Cespugli, Marco, additional, Durmaz, Vedat, additional, Fackeldey, Konstantin, additional, Fischer, Patrick D., additional, Gorgulla, Christoph, additional, Gruber, Christian, additional, Gruber, Karl, additional, Hetmann, Michael, additional, Kinney, Jamie E., additional, Padmanabha Das, Krishna M., additional, Pandita, Shreya, additional, Singh, Amit, additional, Steinkellner, Georg, additional, Tesseyre, Guilhem, additional, Wagner, Gerhard, additional, Wang, Zi-Fu, additional, Yust, Ryan J., additional, Druzhilovskiy, Dmitry S., additional, Filimonov, Dmitry A., additional, Pogodin, Pavel V., additional, Poroikov, Vladimir, additional, Rudik, Anastassia V., additional, Stolbov, Leonid A., additional, Veselovsky, Alexander V., additional, De Rosa, Maria, additional, De Simone, Giada, additional, Gulotta, Maria R., additional, Lombino, Jessica, additional, Mekni, Nedra, additional, Perricone, Ugo, additional, Casini, Arturo, additional, Embree, Amanda, additional, Gordon, D. Benjamin, additional, Lei, David, additional, Pratt, Katelin, additional, Voigt, Christopher A., additional, Chen, Kuang-Yu, additional, Jacob, Yves, additional, Krischuns, Tim, additional, Lafaye, Pierre, additional, Zettor, Agnès, additional, Rodríguez, M. Luis, additional, White, Kris M., additional, Fearon, Daren, additional, Von Delft, Frank, additional, Walsh, Martin A., additional, Horvath, Dragos, additional, Brooks III, Charles L., additional, Falsafi, Babak, additional, Ford, Bryan, additional, García-Sastre, Adolfo, additional, Lee, Sang Yup, additional, Naffakh, Nadia, additional, Varnek, Alexandre, additional, Klambauer, Günter, additional, and Hermans, Thomas M., additional

Published
2023
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2. A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics

Author

Gossen, Jonas, Albani, Simone, Hanke, Anton, Joseph, Benjamin P., Bergh, Cathrine, Kuzikov, Maria, Costanzi, Elisa, Manelfi, Candida, Storici, Paola, Gribbon, Philip, Beccari, Andrea R., Talarico, Carmine, Spyrakis, Francesca, Lindahl, Erik, Zaliani, Andrea, Carloni, Paolo, Wade, Rebecca C., Musiani, Francesco, Kokh, Daria B., Rossetti, Giulia, Gossen, Jonas, Albani, Simone, Hanke, Anton, Joseph, Benjamin P., Bergh, Cathrine, Kuzikov, Maria, Costanzi, Elisa, Manelfi, Candida, Storici, Paola, Gribbon, Philip, Beccari, Andrea R., Talarico, Carmine, Spyrakis, Francesca, Lindahl, Erik, Zaliani, Andrea, Carloni, Paolo, Wade, Rebecca C., Musiani, Francesco, Kokh, Daria B., and Rossetti, Giulia

Abstract

The SARS-CoV-2 coronavirus outbreak continues to spread at a rapid rate worldwide. The main protease (Mpro) is an attractive target for anti-COVID-19 agents. Unexpected difficulties have been encountered in the design of specific inhibitors. Here, by analyzing an ensemble of similar to 30 000 SARS-CoV-2 Mpro conformations from crystallographic studies and molecular simulations, we show that small structural variations in the binding site dramatically impact ligand binding properties. Hence, traditional druggability indices fail to adequately discriminate between highly and poorly druggable conformations of the binding site. By performing similar to 200 virtual screenings of compound libraries on selected protein structures, we redefine the protein's druggability as the consensus chemical space arising from the multiple conformations of the binding site formed upon ligand binding. This procedure revealed a unique SARS-CoV-2 Mpro blueprint that led to a definition of a specific structure-based pharmacophore. The latter explains the poor transferability of potent SARS-CoV Mpro inhibitors to SARS-CoV-2 Mpro, despite the identical sequences of the active sites. Importantly, application of the pharmacophore predicted novel high affinity inhibitors of SARS-CoV-2 Mpro, that were validated by in vitro assays performed here and by a newly solved X-ray crystal structure. These results provide a strong basis for effective rational drug design campaigns against SARS-CoV-2 Mpro and a new computational approach to screen protein targets with malleable binding sites., QC 20210719

Published
2021
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3. A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics

Author

Gossen, Jonas, primary, Albani, Simone, additional, Hanke, Anton, additional, Joseph, Benjamin P., additional, Bergh, Cathrine, additional, Kuzikov, Maria, additional, Costanzi, Elisa, additional, Manelfi, Candida, additional, Storici, Paola, additional, Gribbon, Philip, additional, Beccari, Andrea R., additional, Talarico, Carmine, additional, Spyrakis, Francesca, additional, Lindahl, Erik, additional, Zaliani, Andrea, additional, Carloni, Paolo, additional, Wade, Rebecca C., additional, Musiani, Francesco, additional, Kokh, Daria B., additional, and Rossetti, Giulia, additional

Published
2021
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4. Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen

Author

Kuzikov, Maria, primary, Costanzi, Elisa, additional, Reinshagen, Jeanette, additional, Esposito, Francesca, additional, Vangeel, Laura, additional, Wolf, Markus, additional, Ellinger, Bernhard, additional, Claussen, Carsten, additional, Geisslinger, Gerd, additional, Corona, Angela, additional, Iaconis, Daniela, additional, Talarico, Carmine, additional, Manelfi, Candida, additional, Cannalire, Rolando, additional, Rossetti, Giulia, additional, Gossen, Jonas, additional, Albani, Simone, additional, Musiani, Francesco, additional, Herzog, Katja, additional, Ye, Yang, additional, Giabbai, Barbara, additional, Demitri, Nicola, additional, Jochmans, Dirk, additional, Jonghe, Steven De, additional, Rymenants, Jasper, additional, Summa, Vincenzo, additional, Tramontano, Enzo, additional, Beccari, Andrea R., additional, Leyssen, Pieter, additional, Storici, Paola, additional, Neyts, Johan, additional, Gribbon, Philip, additional, and Zaliani, Andrea, additional

Published
2021
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14. Computational Study of the DNA-Binding ProteinHelicobacter pyloriNikR: The Role of Ni2+2 Francesco Musiani and Branimir Bertoša contributed equally to the simulations presented here.

Author

Musiani, Francesco, primary, Bertoša, Branimir, additional, Magistrato, Alessandra, additional, Zambelli, Barbara, additional, Turano, Paola, additional, Losasso, Valeria, additional, Micheletti, Cristian, additional, Ciurli, Stefano, additional, and Carloni, Paolo, additional

Published
2010
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18. Electron Transfer from HiPIP to the Photooxidized Tetraheme Cytochrome Subunit of Allochromatium vinosum Reaction Center: New Insights from Site-Directed Mutagenesis and Computational Studies

Author

Venturoli, Giovanni, primary, Mamedov, Mahir D., additional, Mansy, Sheref S., additional, Musiani, Francesco, additional, Strocchi, Massimo, additional, Francia, Francesco, additional, Semenov, Alexey Yu., additional, Cowan, James A., additional, and Ciurli, Stefano, additional

Published
2003
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19. Glutamate Ligation in the Ni(II)- and Co(II)-Responsive Escherichia coli Transcriptional Regulator, RcnR

Author

Michael J. Maroney, Hsin-Ting Huang, Francesco Musiani, Peter T. Chivers, Stefano Ciurli, Carolyn E. Carr, Carr, Carolyn E., Musiani, Francesco, Huang, Hsin-Ting, Chivers, Peter T., Ciurli, Stefano, and Maroney, Michael J

Subjects
Models, Molecular, 0301 basic medicine, Molecular model, Stereochemistry, Metal ions in aqueous solution, Glutamic Acid, Repressor, Ligands, medicine.disease_cause, Article, Inorganic Chemistry, Metal, 03 medical and health sciences, Nickel, Organometallic Compounds, medicine, Physical and Theoretical Chemistry, Binding site, Escherichia coli, Binding Sites, Chemistry, Escherichia coli Proteins, Cobalt, Ligand (biochemistry), Repressor Proteins, 030104 developmental biology, visual_art, visual_art.visual_art_medium, Protein ligand
Abstract

Escherichia coli RcnR (resistance to cobalt and nickel regulator, EcRcnR) is a metal-responsive repressor of the genes encoding the Ni(II) and Co(II) exporter proteins RcnAB by binding to PRcnAB. The DNA binding affinity is weakened when the cognate ions Ni(II) and Co(II) bind to EcRcnR in a six-coordinate site that features a (N/O)5S ligand donor-atom set in distinct sites: while both metal ions are bound by the N terminus, Cys35, and His64, Co(II) is additionally bound by His3. On the other hand, the noncognate Zn(II) and Cu(I) ions feature a lower coordination number, have a solvent-accessible binding site, and coordinate protein ligands that do not include the N-terminal amine. A molecular model of apo-EcRcnR suggested potential roles for Glu34 and Glu63 in binding Ni(II) and Co(II) to EcRcnR. The roles of Glu34 and Glu63 in metal binding, metal selectivity, and function were therefore investigated using a structure/function approach. X-ray absorption spectroscopy was used to assess the structural changes in the Ni(II), Co(II), and Zn(II) binding sites of Glu → Ala and Glu → Cys variants at both positions. The effect of these structural alterations on the regulation of PrcnA by EcRcnR in response to metal binding was explored using LacZ reporter assays. These combined studies indicate that while Glu63 is a ligand for both metal ions, Glu34 is a ligand for Co(II) but possibly not for Ni(II). The Glu34 variants affect the structure of the cognate metal sites, but they have no effect on the transcriptional response. In contrast, the Glu63 variants affect both the structure and transcriptional response, although they do not completely abolish the function of EcRcnR. The structure of the Zn(II) site is not significantly perturbed by any of the glutamic acid variations. The spectroscopic and functional data obtained on the mutants were used to calculate models of the metal-site structures of EcRcnR bound to Ni(II), Co(II), and Zn(II). The results are interpreted in terms of a switch mechanism, in which a subset of the metal-binding ligands is responsible for the allosteric response required for DNA release.

Published
2017
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20. Evidence for a Transient Additional Ligand Binding Site in the TAS2R46 Bitter Taste Receptor

Author

Alejandro Giorgetti, Anne Brockhoff, Massimo Sandal, Wolfgang Meyerhof, Paolo Carloni, Francesco Musiani, Maik Behrens, Sandal, Massimo, Behrens, Maik, Brockhoff, Anne, Musiani, Francesco, Giorgetti, Alejandro, Carloni, Paolo, and Meyerhof, Wolfgang

Subjects
Agonist, Homology modeling, Hybrid approaches, GPCR, bitter receptors, Subfamily, medicine.drug_class, Ligand, Molecular Dynamics Simulation, Biology, Ligands, Molecular mechanics, Receptors, G-Protein-Coupled, Hybrid approaches, Structure-Activity Relationship, GPCR, medicine, Humans, Homology modeling, Physical and Theoretical Chemistry, Binding site, Receptor, G protein-coupled receptor, Helix bundle, Binding Sites, Molecular Structure, Medicine (all), Binding Site, Computer Science Applications1707 Computer Vision and Pattern Recognition, Strychnine, bitter receptors, Computer Science Applications, Biochemistry, Biophysics, Human
Abstract

Most human G protein coupled receptors (GPCRs) are activated by small molecules binding to their 7-transmembrane (7-TM) helix bundle. They belong to basally diverging branches: the 25 bitter taste 2 receptors and most members of the very large rhodopsin-like/class A GPCRs subfamily. Some members of the class A branch have been suggested to feature not only an orthosteric agonist-binding site but also a more extracellular or "vestibular" site, involved in the binding process. Here we use a hybrid molecular mechanics/coarse-grained (MM/CG) molecular dynamics approach on a widely studied bitter taste receptor (TAS2R46) receptor in complex with its agonist strychnine. Three ∼1 μs molecular simulation trajectories find two sites hosting the agonist, which together elucidate experimental data measured previously and in this work. This mechanism shares similarities with the one suggested for the evolutionarily distant class A GPCRs. It might be instrumental for the remarkably broad but specific spectrum of agonists of these chemosensory receptors.

Published
2015
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