22 results on '"Amen Shamim"'
Search Results
2. Insights into the Differential Composition of Stem-Loop Structures of Nanoviruses and Their Impacts
- Author
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Aamir Lal, Amen Shamim, Eui-Joon Kil, Thuy T. B. Vo, Muhammad Amir Qureshi, Nattanong Bupi, Marjia Tabassum, and Sukchan Lee
- Subjects
multipartite viruses ,nanoviruses ,molecular dynamics simulation ,common region-stem-loop ,Microbiology ,QR1-502 - Abstract
ABSTRACT Multipartite viruses package their genomic segments independently and mainly infect plants; few of them target animals. Nanoviridae is a family of multipartite single-stranded DNA (ssDNA) plant viruses that individually encapsidate ssDNAs of ~1 kb and transmit them through aphids without replication in aphid vectors, thereby causing important diseases in host plants, mainly leguminous crops. All of these components constitute an open reading frame to perform a specific role in nanovirus infection. All segments contain conserved inverted repeat sequences, potentially forming a stem-loop structure and a conserved nonanucleotide, TAGTATTAC, within a common region. This study investigated the variations in the stem-loop structure of nanovirus segments and their impact using molecular dynamics (MD) simulations and wet lab approaches. Although the accuracy of MD simulations is limited by force field approximations and simulation time scale, explicit solvent MD simulations were successfully used to analyze the important aspects of the stem-loop structure. This study involves the mutants’ design, based on the variations in the stem-loop region and construction of infectious clones, followed by their inoculation and expression analysis, based on nanosecond dynamics of the stem-loop structure. The original stem-loop structures showed more conformational stability than mutant stem-loop structures. The mutant structures were expected to alter the neck region of the stem-loop by adding and switching nucleotides. Changes in conformational stability are suggested expression variations of the stem-loop structures found in host plants with nanovirus infection. However, our results can be a starting point for further structural and functional analysis of nanovirus infection. IMPORTANCE Nanoviruses comprise multiple segments, each with a single open reading frame to perform a specific function and an intergenic region with a conserved stem-loop region. The genome expression of a nanovirus has been an intriguing area but is still poorly understood. We attempted to investigate the variations in the stem-loop structure of nanovirus segments and their impact on viral expression. Our results show that the stem-loop composition is essential in controlling the virus segments' expression level.
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- 2023
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- View/download PDF
3. Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy
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Young Suk Yu, Hijai R. Shin, Dongha Kim, Seon Ah Baek, Seon Ah Choi, Hyejin Ahn, Amen Shamim, Jeonghwan Kim, Ik Soo Kim, Kyeong Kyu Kim, Kyoung-Jae Won, and Sung Hee Baek
- Subjects
Science - Abstract
Epigenetic regulations of autophagy have emerged as mechanisms for maintaining cellular homeostasis. Here the authors reveal that the CARM1-Pontin-FOXO3a signaling axis can activate autophagy related genes through enhancer activation.
- Published
- 2020
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- View/download PDF
4. Functional and Structural Changes in the Membrane-Bound O-Acyltransferase Family Member 7 (MBOAT7) Protein: The Pathomechanism of a Novel MBOAT7 Variant in Patients With Intellectual Disability
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Jiwon Lee, Amen Shamim, Jongho Park, Ja-Hyun Jang, Ji Hye Kim, Jeong-Yi Kwon, Jong-Won Kim, Kyeong Kyu Kim, and Jeehun Lee
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intellectual disability ,MBOAT7 ,autism spectrum disorder ,globus pallidus ,cerebellar dentate nucleus ,molecular modeling ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) gene is associated with intellectual disability, early onset seizures, and autism spectrum disorders. This study aimed to determine the pathogenetic mechanism of the MBOAT7 missense variant via molecular modeling. Three patients from a consanguineous family were found to have a homozygous c.757G>A (p.Glu253Lys) variant of MBOAT7. The patients showed prominent dysfunction in gait, swallowing, vocalization, and fine motor function and had intellectual disabilities. Brain magnetic resonance imaging showed signal changes in the bilateral globus pallidi and cerebellar dentate nucleus, which differed with age. In the molecular model of human MBOAT7, Glu253 in the wild-type protein is located close to the backbone carbonyl oxygens in the loop near the helix, suggesting that the ionic interaction could contribute to the conformational stability of the funnel. Molecular modeling showed that Lys253 in the mutant protein was expected to alter the surface charge distribution, thereby potentially affecting substrate specificity. Changes in conformational stability and substrate specificity through varied ionic interactions are the suggested pathophysiological mechanisms of the MBOAT7 variant found in patients with intellectual disabilities.
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- 2022
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- View/download PDF
5. Analysis of Novel Drug-Resistant Human Cytomegalovirus DNA Polymerase Mutations Reveals the Role of a DNA-Binding Loop in Phosphonoformic Acid Resistance
- Author
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Kye Ryeong Park, Young-Eui Kim, Amen Shamim, Shuang Gong, Soo-Han Choi, Kyeong Kyu Kim, Yae-Jean Kim, and Jin-Hyun Ahn
- Subjects
HCMV ,polymerase ,drug ,phosphonoacetic acid ,mutation ,Microbiology ,QR1-502 - Abstract
The appearance of drug-resistant mutations in UL54 DNA polymerase and UL97 kinase genes is problematic for the treatment of human cytomegalovirus (HCMV) diseases. During treatment of HCMV infection in a pediatric hematopoietic cell transplant recipient, H600L and T700A mutations and E576G mutation were independently found in the UL54 gene. Foscarnet (FOS; phosphonoformic acid) resistance by T700A mutation is reported. Here, we investigated the role of novel mutations in drug resistance by producing recombinant viruses and a model polymerase structure. The H600L mutant virus showed an increase in resistance to ganciclovir (GCV) by 11-fold and to FOS and cidofovir (CDV) by 5-fold, compared to the wild type, while the E756G mutant virus showed an increase in resistance to FOS by 9-fold and modestly to CDV by 2-fold. With the FOS-resistant T700A mutation, only H600L produced increased FOS resistance up to 37-fold, indicating an additive effect of these mutations on FOS resistance. To gain insight into drug resistance mechanisms, a model structure for UL54 polymerase was constructed using the yeast DNA polymerase as a template. In this model, HCMV DNA polymerase contains a long palm loop domain of which H600 and T700 are located on each end and T700 interacts with the FOS binding pocket. Our results demonstrate that H600L and E756G mutations in UL54 polymerase are novel drug-resistant mutations and that the acquisition of both H600L and T700A mutations in the DNA-binding loop confers increased resistance to FOS treatment, providing novel insights for the mechanism acquiring foscarnet resistance.
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- 2022
- Full Text
- View/download PDF
6. Genome-Wide Analysis of Staphylococcus aureus Sequence Type 72 Isolates Provides Insights Into Resistance Against Antimicrobial Agents and Virulence Potential
- Author
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Nayab Batool, Amen Shamim, Akhilesh Kumar Chaurasia, and Kyeong Kyu Kim
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Staphylococcus aureus ,sequence type 72 ,antibiotics resistance ,virulence factors ,subtractive genomics ,Microbiology ,QR1-502 - Abstract
Staphylococcus aureus sequence type 72 (ST72) is a major community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) that has rapidly entered the hospital setting in Korea, causing mild superficial skin wounds to severe bloodstream infections. In this study, we sequenced and analyzed the genomes of one methicillin-resistant human isolate and one methicillin-sensitive human isolate of ST72 from Korea, K07-204 and K07-561, respectively. We used a subtractive genomics approach to compare these two isolates to other 27 ST72 isolates to investigate antimicrobial resistance (AMR) and virulence potential. Furthermore, we validated genotypic differences by phenotypic characteristics analysis. Comparative and subtractive genomics analysis revealed that K07-204 contains methicillin (mecA), ampicillin (blaZ), erythromycin (ermC), aminoglycoside (aadD), and tetracycline (tet38, tetracycline efflux pump) resistance genes while K07-561 has ampicillin (blaZ) and tetracycline (tet38) resistance genes. In addition to antibiotics, K07-204 was reported to show resistance to lysostaphin treatment. K07-204 also has additional virulence genes (adsA, aur, hysA, icaABCDR, lip, lukD, sdrC, and sdrE) compared to K07-561, which may explain the differential virulence potential of these human isolates of ST72. Unexpectedly, the virulence potential of K07-561 was higher in an in vivo wax-worm infection model than that of K07-204, putatively due to the presence of a 20-fold higher staphyloxanthin concentration than K07-204. Comprehensive genomic analysis of these two human isolates, with 27 ST72 isolates, and S. aureus USA300 (ST8) suggested that acquisition of both virulence and antibiotics resistance genes by ST72 isolates might have facilitated their adaptation from a community to a hospital setting where the selective pressure imposed by antibiotics selects for more resistant and virulent isolates. Taken together, the results of the current study provide insight into the genotypic and phenotypic features of various ST72 clones across the globe, delivering more options for developing therapeutics and rapid molecular diagnostic tools to detect resistant bacteria.
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- 2021
- Full Text
- View/download PDF
7. MD-TSPC4: Computational Method for Predicting the Thermal Stability of I-Motif
- Author
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Amen Shamim, Maria Razzaq, and Kyeong Kyu Kim
- Subjects
i-motifs ,molecular dynamics simulation ,melting temperature ,CD spectroscopy ,thermal stability ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
I-Motif is a tetrameric cytosine-rich DNA structure with hemi-protonated cytosine: cytosine base pairs. Recent evidence showed that i-motif structures in human cells play regulatory roles in the genome. Therefore, characterization of novel i-motifs and investigation of their functional implication are urgently needed for comprehensive understanding of their roles in gene regulation. However, considering the complications of experimental investigation of i-motifs and the large number of putative i-motifs in the genome, development of an in silico tool for the characterization of i-motifs in the high throughput scale is necessary. We developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic simulation. By assuming that the flexibility of loops in i-motifs correlated with thermal stability within certain temperature ranges, we evaluated the correlation between the root mean square deviations (RMSDs) of model structures and the thermal stability as the experimentally obtained melting temperature (Tm). Based on this correlation, we propose an equation for Tm prediction from RMSD. We expect this method can be useful for estimating the overall structure and stability of putative i-motifs in the genome, which can be a starting point of further structural and functional studies of i-motifs.
- Published
- 2020
- Full Text
- View/download PDF
8. Molecular Packing Interaction in DNA Crystals
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Amen Shamim, Nazia Parveen, Vinod Kumar Subramani, and Kyeong Kyu Kim
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DNA ,crystal structures ,crystal packing ,crystallography ,terminal end ,base ,Crystallography ,QD901-999 - Abstract
DNA crystallography provides essential structural information to understand the biochemical and biological functions of oligonucleotides. Therefore, it is necessary to understand the factors affecting crystallization of DNA to develop a strategy for production of diffraction-quality DNA crystals. We analyzed key factors affecting intermolecular interactions in 509 DNA crystals from the Nucleic Acid Database and Protein Databank. Packing interactions in DNA crystals were classified into four categories based on the intermolecular hydrogen bonds in base or backbone, and their correlations with other factors were analyzed. From this analysis, we confirmed that hydrogen bonding between terminal end and mid-region is most common in crystal packing and in high-resolution crystal structures. Interestingly, P212121 is highly preferred in DNA crystals in general, but the P61 space group is relatively abundant in A-DNA crystals. Accordingly, P212121 contains more terminal end-mid-region interactions than other space groups, confirming the significance of this interaction. While metals play a role in the production of a good crystal in B-DNA conformation, their effect is not significant in other conformations. From these analyses, we found that packing interaction and other factors have a strong influence on the quality of DNA crystals and provide key information to predict crystal growth of candidate oligonucleotides.
- Published
- 2020
- Full Text
- View/download PDF
9. Study of Biochemical Changes and Elevated Levels of Enzymes in Salmonella typhi Infected Patients in Pakistani Population
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Ayesha Shamim, Bilal Hussain, and Amen Shamim
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Biochemical ,Typhoid fever ,Hepatic enzyme ,Biology (General) ,QH301-705.5 - Abstract
Typhoid fever causes significant biochemical changes and hepatic complications. As many studies have indicated several biochemical parameters that are involved in developing the risk of typhoid fever. The current study was designed to evaluate these risk factors in general Pakistani population. Serum biochemistry and liver enzymes were studied to investigate the relationship of these risk factors to Typhoid fever. Total 100 subjects were studied, 50 healthy individuals and 50 typhoid patients. Blood samples were collected from Allied and National Hospital, Faisalabad, Pakistan. In this study, Nested PCR was used to test the samples. Elevated level of ALT (P
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- 2012
10. The SHERLOCK Platform: An Insight into Advances in Viral Disease Diagnosis
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Ambreen Zahra, Ayesha Shahid, Amen Shamim, Sultan Habibullah Khan, and Muhammad Imran Arshad
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Bioengineering ,Molecular Biology ,Applied Microbiology and Biotechnology ,Biochemistry ,Biotechnology - Abstract
Persistence and prevalence of microbial diseases (pandemics, epidemics) is the most alarming threats to the human resulting in huge health and economic losses. Rapid detection and understanding of the disease dynamics by molecular biotechnology tools allow for robust reporting, treatment and control of diseases. As per WHO, the optimal diagnostic approach should be quick, specific, sensitive, without a stringed instrument, and low cost. The drawbacks of traditional detection techniques promote the use of CRISPR-mediated nucleic acid detection methods such as SHERLOCK as detection method. It takes advantage of the unexpected in vitro features of CRISPR-Cas system to develop field-deployable sensitive detection tools. Previously, CRISPR-mediated diagnostic methods have extensively been reviewed particularly for SARS-COV-2 detection, but it fails to provide the insight into advances of this technique. This study is the first attempt to review the advances of SHERLOCK approach as diagnostic tool for viral diseases detection. Variations of SHERLOCK mechanism for improved efficiency are discussed. Particularly integrated SHERLOCK approaches in terms of extraction-free assay and Bluetooth-enabled detection are reviewed to access their feasibility for the development of simpler and cost-effective diagnostic toolkits. Insight in to perks and limitations of diagnostic methods indicates its potential as ultimate diagnostic instrument for disease management.
- Published
- 2022
11. AC-motif: a DNA motif containing adenine and cytosine repeat plays a role in gene regulation
- Author
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Sungjin Lee, Jihyeon Yu, Wanki Yoo, Sangsu Bae, Chan Young Kang, Kyeong Kyu Kim, Amen Shamim, Ambarnil Ghosh, Jeong Hwan Hur, Nazia Parveen, and Chin-Ju Park
- Subjects
AcademicSubjects/SCI00010 ,Stereochemistry ,Base pair ,Protein Serine-Threonine Kinases ,Biology ,Genome ,Cytosine ,chemistry.chemical_compound ,Structural Biology ,Genetics ,Humans ,Magnesium ,A-DNA ,Nucleotide Motifs ,Promoter Regions, Genetic ,Base Pairing ,Protein secondary structure ,Magnesium ion ,Gene Editing ,Regulation of gene expression ,Base Sequence ,Adenine ,DNA ,G-Quadruplexes ,Gene Expression Regulation ,Oligodeoxyribonucleotides ,chemistry ,Nucleic Acid Conformation - Abstract
I-motif or C4 is a four-stranded DNA structure with a protonated cytosine:cytosine base pair (C+:C) found in cytosine-rich sequences. We have found that oligodeoxynucleotides containing adenine and cytosine repeats form a stable secondary structure at a physiological pH with magnesium ion, which is similar to i-motif structure, and have named this structure ‘adenine:cytosine-motif (AC-motif)’. AC-motif contains C+:C base pairs intercalated with putative A+:C base pairs between protonated adenine and cytosine. By investigation of the AC-motif present in the CDKL3 promoter (AC-motifCDKL3), one of AC-motifs found in the genome, we confirmed that AC-motifCDKL3 has a key role in regulating CDKL3 gene expression in response to magnesium. This is further supported by confirming that genome-edited mutant cell lines, lacking the AC-motif formation, lost this regulation effect. Our results verify that adenine-cytosine repeats commonly present in the genome can form a stable non-canonical secondary structure with a non-Watson–Crick base pair and have regulatory roles in cells, which expand non-canonical DNA repertoires.
- Published
- 2021
12. Detection of SARS-CoV-2 by RT-LAMP assay in Human COVID-19 patients
- Author
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Waqas Rafique Ali, Ambreen Zahra, Hamza Rasheed, Aqsa Ahmad, Sultan Habibullah Khan, Amen Shamim, Sabin Aslam, and Muhammad Imran Arshad
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- 2022
13. Functional and Structural Changes in the Membrane-Bound O-Acyltransferase Family Member 7 (MBOAT7) Protein: The Pathomechanism of a Novel
- Author
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Jiwon, Lee, Amen, Shamim, Jongho, Park, Ja-Hyun, Jang, Ji Hye, Kim, Jeong-Yi, Kwon, Jong-Won, Kim, Kyeong Kyu, Kim, and Jeehun, Lee
- Abstract
The membrane-bound O-acyltransferase domain-containing 7
- Published
- 2021
14. Analysis of Novel Drug-Resistant Human Cytomegalovirus DNA Polymerase Mutations Reveals the Role of a DNA-Binding Loop in Phosphonoformic Acid Resistance
- Author
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Kye Ryeong Park, Young-Eui Kim, Amen Shamim, Shuang Gong, Soo-Han Choi, Kyeong Kyu Kim, Yae-Jean Kim, and Jin-Hyun Ahn
- Subjects
Microbiology (medical) ,polymerase ,viruses ,phosphonoacetic acid ,virus diseases ,drug ,mutation ,Microbiology ,HCMV ,QR1-502 - Abstract
The appearance of drug-resistant mutations in UL54 DNA polymerase and UL97 kinase genes is problematic for the treatment of human cytomegalovirus (HCMV) diseases. During treatment of HCMV infection in a pediatric hematopoietic cell transplant recipient, H600L and T700A mutations and E576G mutation were independently found in the UL54 gene. Foscarnet (FOS; phosphonoformic acid) resistance by T700A mutation is reported. Here, we investigated the role of novel mutations in drug resistance by producing recombinant viruses and a model polymerase structure. The H600L mutant virus showed an increase in resistance to ganciclovir (GCV) by 11-fold and to FOS and cidofovir (CDV) by 5-fold, compared to the wild type, while the E756G mutant virus showed an increase in resistance to FOS by 9-fold and modestly to CDV by 2-fold. With the FOS-resistant T700A mutation, only H600L produced increased FOS resistance up to 37-fold, indicating an additive effect of these mutations on FOS resistance. To gain insight into drug resistance mechanisms, a model structure for UL54 polymerase was constructed using the yeast DNA polymerase as a template. In this model, HCMV DNA polymerase contains a long palm loop domain of which H600 and T700 are located on each end and T700 interacts with the FOS binding pocket. Our results demonstrate that H600L and E756G mutations in UL54 polymerase are novel drug-resistant mutations and that the acquisition of both H600L and T700A mutations in the DNA-binding loop confers increased resistance to FOS treatment, providing novel insights for the mechanism acquiring foscarnet resistance.
- Published
- 2021
15. Computational Approaches to Predict the Non-canonical DNAs
- Author
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Seunghee Cho, Kyeong Kyu Kim, Amen Shamim, and Nazia Parveen
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0303 health sciences ,03 medical and health sciences ,Computational Mathematics ,0302 clinical medicine ,Non canonical ,030220 oncology & carcinogenesis ,Genetics ,Statistical physics ,Biology ,Molecular Biology ,Biochemistry ,030304 developmental biology - Abstract
Background:Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA.Objective:Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs.Conclusion:There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.
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- 2019
16. Bioinformatics–computer programming
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Muhammad Sarmad Iftikhar, Amen Shamim, Muqadas Aleem, and Ghulam Mohyuddin Talha
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business.industry ,Computer programming ,Cancer ,Abnormal cell ,Disease ,Gene mutation ,Biology ,Bioinformatics ,medicine.disease ,chemistry.chemical_compound ,chemistry ,medicine ,Epigenetics ,business ,DNA - Abstract
Cancer is the sum of about 277 different forms of cancer disease. It has been found that gene mutations or genetic disorders caused by genetic and epigenetic factors lead toward abnormal cell proliferation which is said to be cancer. Advances in technology have provided us with increases knowledge of DNA, RNA, and proteins being studied in cancer tissues through advanced bioinformatics tools. This chapter provides an overview of bioinformatics techniques being used in cancer research. There was a need to understand different cancer types, diagnosis, and cure; for which bioinformatics could be a much better tool. Cancer being the most devastating disease is spreading fast in our communities. Modern-day techniques produce a large amount of data that needs high-throughput techniques to arrange, handle and analyze. Bioinformatics tools provide this platform to better understand, analyze and interpret this data. At the end of the chapter, the techniques have been explained with some examples where these were used successfully.
- Published
- 2021
17. Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy
- Author
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Amen Shamim, Jeonghwan Kim, Sung Hee Baek, Dong Ha Kim, Hijai R. Shin, Hyejin Ahn, Kyeong Kyu Kim, Seon Ah Baek, Ik Soo Kim, Seon Ah Choi, Kyoung-Jae Won, and Young Suk Yu
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0301 basic medicine ,Protein-Arginine N-Methyltransferases ,Molecular biology ,General Physics and Astronomy ,Biochemistry ,Transgenic ,Epigenesis, Genetic ,Histones ,Mice ,Gene Knockout Techniques ,0302 clinical medicine ,Multidisciplinary ,Forkhead Box Protein O3 ,food and beverages ,Acetylation ,Hep G2 Cells ,Methylation ,Cell biology ,Gene Knockdown Techniques ,Signal Transduction ,Transcriptional Activation ,CARM1 ,1.1 Normal biological development and functioning ,Science ,Mice, Transgenic ,Biology ,Arginine ,Article ,Lysine Acetyltransferase 5 ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Genetic ,Underpinning research ,Autophagy ,Genetics ,Animals ,Humans ,Epigenetics ,Enhancer ,Protein Processing ,HEK 293 cells ,DNA Helicases ,Post-Translational ,General Chemistry ,Histone acetyltransferase ,Fibroblasts ,Glucose ,HEK293 Cells ,030104 developmental biology ,Hela Cells ,Trans-Activators ,biology.protein ,ATPases Associated with Diverse Cellular Activities ,Generic health relevance ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery ,HeLa Cells ,Epigenesis - Abstract
Autophagy is a catabolic process through which cytoplasmic components are degraded and recycled in response to various stresses including starvation. Recently, transcriptional and epigenetic regulations of autophagy have emerged as essential mechanisms for maintaining homeostasis. Here, we identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Genome-wide analyses and biochemical studies reveal that methylated Pontin functions as a platform for recruiting Tip60 histone acetyltransferase with increased H4 acetylation and subsequent activation of autophagy genes regulated by FOXO3a. Surprisingly, CARM1-Pontin-FOXO3a signaling axis can work in the distal regions and activate autophagy genes through enhancer activation. Together, our findings provide a signaling axis of CARM1-Pontin-FOXO3a and further expand the role of CARM1 in nuclear regulation of autophagy., Epigenetic regulations of autophagy have emerged as mechanisms for maintaining cellular homeostasis. Here the authors reveal that the CARM1-Pontin-FOXO3a signaling axis can activate autophagy related genes through enhancer activation.
- Published
- 2020
18. Molecular Packing Interaction in DNA Crystals
- Author
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Kyeong Kyu Kim, Nazia Parveen, Vinod Kumar Subramani, and Amen Shamim
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0301 basic medicine ,General Chemical Engineering ,Crystal structure ,010402 general chemistry ,01 natural sciences ,law.invention ,Inorganic Chemistry ,Crystal ,03 medical and health sciences ,chemistry.chemical_compound ,crystal structures ,law ,lcsh:QD901-999 ,General Materials Science ,base ,Crystallization ,crystallography ,Hydrogen bond ,Oligonucleotide ,Intermolecular force ,DNA ,Condensed Matter Physics ,0104 chemical sciences ,Crystallography ,030104 developmental biology ,chemistry ,terminal end ,sugar-phosphate backbone ,Nucleic acid ,lcsh:Crystallography ,crystal packing - Abstract
DNA crystallography provides essential structural information to understand the biochemical and biological functions of oligonucleotides. Therefore, it is necessary to understand the factors affecting crystallization of DNA to develop a strategy for production of diffraction-quality DNA crystals. We analyzed key factors affecting intermolecular interactions in 509 DNA crystals from the Nucleic Acid Database and Protein Databank. Packing interactions in DNA crystals were classified into four categories based on the intermolecular hydrogen bonds in base or backbone, and their correlations with other factors were analyzed. From this analysis, we confirmed that hydrogen bonding between terminal end and mid-region is most common in crystal packing and in high-resolution crystal structures. Interestingly, P212121 is highly preferred in DNA crystals in general, but the P61 space group is relatively abundant in A-DNA crystals. Accordingly, P212121 contains more terminal end-mid-region interactions than other space groups, confirming the significance of this interaction. While metals play a role in the production of a good crystal in B-DNA conformation, their effect is not significant in other conformations. From these analyses, we found that packing interaction and other factors have a strong influence on the quality of DNA crystals and provide key information to predict crystal growth of candidate oligonucleotides.
- Published
- 2020
- Full Text
- View/download PDF
19. MD-TSPC4: Computational Method for Predicting the Thermal Stability of I-Motif
- Author
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Maria Razzaq, Amen Shamim, and Kyeong Kyu Kim
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0301 basic medicine ,Molecular model ,Base pair ,In silico ,i-motifs ,Quantitative Structure-Activity Relationship ,Molecular Dynamics Simulation ,010402 general chemistry ,01 natural sciences ,Genome ,melting temperature ,Catalysis ,Article ,thermal stability ,Inorganic Chemistry ,Root mean square ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,Cytosine ,Humans ,Thermal stability ,Physical and Theoretical Chemistry ,Nucleotide Motifs ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Physics ,Organic Chemistry ,CD spectroscopy ,Reproducibility of Results ,General Medicine ,DNA ,0104 chemical sciences ,Computer Science Applications ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Nucleic Acid Conformation ,Thermodynamics ,Biological system ,Software - Abstract
I-Motif is a tetrameric cytosine-rich DNA structure with hemi-protonated cytosine: cytosine base pairs. Recent evidence showed that i-motif structures in human cells play regulatory roles in the genome. Therefore, characterization of novel i-motifs and investigation of their functional implication are urgently needed for comprehensive understanding of their roles in gene regulation. However, considering the complications of experimental investigation of i-motifs and the large number of putative i-motifs in the genome, development of an in silico tool for the characterization of i-motifs in the high throughput scale is necessary. We developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic simulation. By assuming that the flexibility of loops in i-motifs correlated with thermal stability within certain temperature ranges, we evaluated the correlation between the root mean square deviations (RMSDs) of model structures and the thermal stability as the experimentally obtained melting temperature (Tm). Based on this correlation, we propose an equation for Tm prediction from RMSD. We expect this method can be useful for estimating the overall structure and stability of putative i-motifs in the genome, which can be a starting point of further structural and functional studies of i-motifs.
- Published
- 2020
20. Identification of potent inhibitors for chromodomain-helicase- DNA-binding protein 1-like through moleculardocking studies
- Author
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Abdul Wadood, Syed Sikander Azam, Amen Shamim, and Sundus Iqbal
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0301 basic medicine ,biology ,Chemistry ,Binding protein ,Organic Chemistry ,Active site ,010402 general chemistry ,Ligand (biochemistry) ,01 natural sciences ,0104 chemical sciences ,Chromodomain ,Chromatin ,03 medical and health sciences ,030104 developmental biology ,Biochemistry ,biology.protein ,Protein function prediction ,Homology modeling ,General Pharmacology, Toxicology and Pharmaceutics ,Protein ligand - Abstract
Chromodomain-helicase-DNA-binding protein 1-like is a chromodomain-containing protein in the SNF2-like family of ATPases. It has the capability to sustain proliferation in cell, encourage tumor growth and prevent apoptosis of cell. The goal of the current study is to build an in silico homology model further to identify the structural features that influence the inhibitory activity of chromodomain-helicase-DNA-binding protein 1-like protein grounded on a variety of 103 set of compounds. GOLD program is used to carry out molecular docking studies to ascertain the binding mode of structurally varied inhibitors of chromodomain-helicase-DNA-binding protein 1-like protein. Most active residues docked with chromodomain-helicase-DNA-binding protein 1-like protein are compound 20, 103 and 22 with their GOLD Scores 90.5, 81.01 and 79.2, respectively. These docked residues exhibited substantial interaction with active site residues of the protein. Ligand-protein binding is further elucidated with the extensive hydrogen bonding and other hydrophobic interactions. Chromodomain-helicase-DNA-binding protein 1-like protein belongs to Snf2 family of proteins with conserved evolutionary function. Another interesting aspect of this study is the presence of a conserved Snf2 N-terminal domain observed in chromodomain-helicase-DNA-binding protein 1-like protein. It controls the catalytic and the helicase activity which is crucial in regulating tumor progression. A hundred nanosecond molecular dynamics simulation of docked chromodomain-helicase-DNA-binding protein 1-like illustrated a stable binding pattern of ligand in the protein’s active site. Furthermore, trajectory analysis was performed to assess various characteristics of the docked system in terms of function of time. This study pinpoints potential novel inhibitors against chromodomain-helicase-DNA-binding protein 1-like protein which have not been reported previously but are involved in the overexpression in different cancers. This finding will help to design a prospective drug for varied number of cancers.
- Published
- 2016
21. Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations
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Sumra Wajid Abbasi, Amen Shamim, and Syed Sikander Azam
- Subjects
Models, Molecular ,Stereochemistry ,Protein Conformation ,In silico ,Molecular Sequence Data ,Molecular Dynamics Simulation ,Protein Structure, Secondary ,chemistry.chemical_compound ,Bacterial Proteins ,Catalytic Domain ,Catalytic triad ,3-Oxoacyl-(Acyl-Carrier-Protein) Synthase ,Materials Chemistry ,Amino Acid Sequence ,Physical and Theoretical Chemistry ,Spectroscopy ,Binding Sites ,biology ,Molecular Structure ,Sequence Homology, Amino Acid ,Protein Stability ,Streptococcus gordonii ,Active site ,Ligand (biochemistry) ,biology.organism_classification ,Computer Graphics and Computer-Aided Design ,Molecular Docking Simulation ,Metabolic pathway ,Biochemistry ,chemistry ,Docking (molecular) ,Drug Design ,biology.protein ,Acyl Coenzyme A ,Lead compound ,Dimerization ,Sequence Alignment ,Protein Binding - Abstract
β-Ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of new antibacterial agents which can overcome the multidrug resistance. Unraveling the fatty acid biosynthesis (FAB) metabolic pathway and understanding structural coordinates of FabH will provide valuable insights to target Streptococcus gordonii for curing oral infection. In this study, we designed inhibitors against therapeutic target FabH, in order to block the FAB pathway. As compared to other targets, FabH has more interactions with other proteins, located on the leading strand with higher codon adaptation index value and associated with lipid metabolism category of COG. Current study aims to gain in silico insights into the structural and dynamical aspect of S. gordonii FabH via molecular docking and molecular dynamics (MD) simulations. The FabH protein is catalytically active in dimerization while it can lock in monomeric state. Current study highlights two residues Pro88 and Leu315 that are close to each other by dimerization. The active site of FabH is composed of the catalytic triad formed by residues Cys112, His249, and Asn279 in which Cys112 is involved in acetyl transfer, while His249 and Asn279 play an active role in decarboxylation. Docking analysis revealed that among the studied compounds, methyl-CoA disulfide has highest GOLD score (82.75), binding affinity (-11 kcal/mol) and exhibited consistently better interactions. During MD simulations, the FabH structure remained stable with the average RMSD value of 1.7 A and 1.6 A for undocked protein and docked complex, respectively. Further, crucial hydrogen bonding of the conserved catalytic triad for exhibiting high affinity between the FabH protein and ligand is observed by RDF analysis. The MD simulation results clearly demonstrated that binding of the inhibitor with S. gordonii FabH enhanced the structure and stabilized the dimeric FabH protein. Therefore, the inhibitor has the potential to become a lead compound.
- Published
- 2014
22. An insight into the exploration of druggable genome of Streptococcus gordonii for the identification of novel therapeutic candidates
- Author
-
Syed Sikander Azam and Amen Shamim
- Subjects
Comparative genomics ,Drug ,biology ,Drug discovery ,media_common.quotation_subject ,In silico ,Streptococcus gordonii ,Druggability ,Computational biology ,Bioinformatics ,biology.organism_classification ,Genome ,Anti-Bacterial Agents ,stomatognathic system ,Drug development ,Drug Discovery ,Genetics ,Metabolome ,Computer Simulation ,Genome, Bacterial ,media_common - Abstract
The discovery of novel drug targets of a genome that can bind with high affinity to drug-like compounds is a significant challenge in drug development. Streptococcus gordonii initiates dental plaque formation and endocarditis by entering into the blood stream, usually after oral trauma. The prolonged use of antibiotics is raising a problem of multi-drug resistance and lack of an optimal therapeutic regime that necessitates the drug discovery of vital importance in curing various infections. To overcome this dilemma, the in silico approach paves the way for identification and qualitative characterization of promising drug targets for S. gordonii that encompass three phases of analyses. The present study deciphers drug target genomes of S. gordonii in which 93 proteins were identified as potential drug targets and 16 proteins were found to be involved in unique metabolic pathways. Highlighted information will convincingly render to facilitate selection of S. gordonii proteins for successful entry into drug design pipelines.
- Published
- 2014
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