A5066696283- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- thermodynamics and calorimetric analyses
- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Animal Disease Management and Epidemiology
- RNA and protein synthesis mechanisms
- Advanced Thermodynamics and Statistical Mechanics
- Spectroscopy and Quantum Chemical Studies
- Chemical Reactions and Isotopes
- Eosinophilic Disorders and Syndromes
- Viral gastroenteritis research and epidemiology
- Click Chemistry and Applications
- Enzyme Production and Characterization
- Mass Spectrometry Techniques and Applications
- Viral Infections and Vectors
- Zoonotic diseases and public health
- Receptor Mechanisms and Signaling
- Inflammasome and immune disorders
- Quantum Information and Cryptography
- Cell Image Analysis Techniques
- Autoimmune and Inflammatory Disorders Research
- Chronic Myeloid Leukemia Treatments
- Salmonella and Campylobacter epidemiology
National Institutes of Health
2015-2024
University of Montana
2021-2024
West Bengal University of Animal and Fishery Sciences
2024
National Institute of Allergy and Infectious Diseases
2019-2024
Rocky Mountain Biological Laboratory
2019
Naval Research Laboratory Information Technology Division
2019
Purdue University West Lafayette
2011-2018
Center for Cancer Research
2014-2015
Centre of Biotechnology of Sfax
2003-2007
Cornell University
2006
Disordered protein-protein interactions (PPIs), those involving a folded protein and an intrinsically disordered (IDP), are prevalent in the cell, including important signaling regulatory pathways. IDPs do not adopt single dominant structure isolation but often become ordered upon binding. To aid understanding of molecular mechanisms PPIs, it is crucial to obtain tertiary PPIs. However, experimental methods have difficulty solving PPIs existing protein-peptide docking able model them. Here...
Polyploidy is the presence of more than two homologous sets chromosomes. It has been one strong driving forces for higher plant evolution and also significant transforming tool breeding programs. The review deals with involvement natural artificial polyploids in enhancing traits diversifying species plants. Artificial polyploidy induction (APPI) mainly done using antimitotic agents like colchicine, trifluralin, oryzalin. This very highly utilized improving yield tolerance to biotic abiotic...
Abstract Arthropod - and vertebrate-associated jingmenviruses (arbo-JMV) have segmented positive-strand RNA genomes are provisional members of the genus Orthoflavivirus (family Flaviviridae ). Current investigations described arbo-JMV infection in vertebrate hosts proximity to humans. This raises concerns about virus host range public health implications. review explores genomic evolutionary relationship between orthoflaviviruses evaluates potential pose a threat.
Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number protein complex structures have been determined using experimental methods, relatively fewer studies performed to determine assembly order complexes. In addition insights into molecular mechanisms function provided by structure a complex, knowing is important for understanding process formation. Assembly also practically useful constructing subcomplexes as step toward solving...
The COVID-19 pandemic continues to pose a substantial threat human lives and is likely do so for years come. Despite the availability of vaccines, searching efficient small-molecule drugs that are widely available, including in low- middle-income countries, an ongoing challenge. In this work, we report results open science community effort, "Billion molecules against challenge", identify inhibitors SARS-CoV-2 or relevant receptors. Participating teams used wide variety computational methods...
Human rhinovirus (HRV) and other members of the enterovirus genus bind small-molecule antiviral compounds in a cavity buried within viral capsid protein VP1. These block release VP4 RNA from inside during uncoating process. In addition, prevent “breathing” motions, transient externalization N-terminal regions VP1 intact capsid. The site for VP1/VP4 or is likely between protomers, distant to binding compounds. Molecular dynamics simulations were conducted explore how compound, WIN 52084,...
The SARS-CoV2 pandemic has highlighted the importance of efficient and effective methods for identification therapeutic drugs, in particular laid bare need that allow exploration full diversity synthesizable small molecules. While classical high-throughput screening may consider up to millions molecules, virtual hold promise enabling appraisal billions candidate thus expanding search space while concurrently reducing costs speeding discovery. Here, we describe a new pipeline, called...
Background Molecular Dynamics (MD) simulation of biomolecules provides important insights into conformational changes and dynamic behavior, revealing critical information about folding interactions with other molecules. This enables advances in drug discovery the design therapeutic interventions. The collection simulations stored computers across world holds immense potential to serve as training data for future Machine Learning models that will transform prediction structure, dynamics,...
Proteins with a modular architecture of multiple domains connected by linkers often exhibit diversity in the relative positions domains, while domain tertiary structure remains unchanged. The biological function these proteins, or regulation their activity, depends on variation orientation and separation. Accordingly, careful characterization interdomain motion correlated fluctuations multidomain systems is relevant for understanding functional behavior proteins. Molecular dynamics (MD)...
ABSTRACT We report the performance of protein–protein docking predictions by our group for recent rounds Critical Assessment Prediction Interactions (CAPRI), a community‐wide assessment state‐of‐the‐art methods. Our prediction procedure uses program named LZerD developed in group. represents protein surface with 3D Zernike descriptors (3DZD), which are based on mathematical series expansion function. The appropriate soft representation 3DZD makes method more tolerant to conformational change...
Computational approaches for small-molecule drug discovery now regularly scale to the consideration of libraries containing billions candidate small molecules. One promising approach increased speed evaluating billion-molecule is develop succinct representations each molecule that enable rapid identification molecules with similar properties. Molecular fingerprints are thought provide a mechanism producing such representations. Here, we explore utility commonly used in context predicting...
We asses the ability of a distance correlation coefficient (DiCC), calculated from covariance, for detecting long-range concerted motion in proteins. establish set criteria ideal values based on determination multidimension, R2. compare detail DiCC and conventional coefficients against these criteria. demonstrate that, contrast to coefficients, which capture long-distance adequately only with certain restrictions reflects appropriate both one-dimension multidimensions. Finally, we usefulness...
The potential for reliably predicting relative binding enthalpies, ΔΔE, from a direct method utilizing molecular dynamics is examined system of three phosphotyrosyl peptides to protein receptor, the Src SH2 domain. enthalpies were calculated energy differences between bound and unbound end-states each peptide equilibrium simulations in explicit water. statistical uncertainties ensemble-mean values multiple, independent obtained using bootstrap method. Simulations initiated with different...
Although prion protein fibrils can have either parallel-in-register intermolecular β-sheet (PIRIBS) or, probably, β-solenoid architectures, the plausibility of PIRIBS architectures for usually glycosylated natural strains has been questioned based expectation that such glycans would not fit if stacked in-register on each monomer within a fibril. To directly assess this issue, we added N-linked to recently reported cryo-electron microscopy-based human amyloid model with architecture and...
Molecular Dynamics (MD) simulation of biomolecules provides important insights into conformational changes and dynamic behavior, revealing critical information about folding interactions with other molecules. The collection simulations stored in computers across the world holds immense potential to serve as training data for future Machine Learning models that will transform prediction structure, dynamics, drug interactions, more. Ideally, there should exist an open access repository enables...
Epstein-Barr virus (EBV) infects B cells and ~95% of adults are infected. EBV glycoprotein gp42 is essential for entry into cells. binds to the β1 chain HLA-DQ, -DR, -DP on cells, uses these molecules infection. To investigate if certain HLA-DQ alleles associated with seronegativity, we recruited ~3,300 healthy adult blood donors, identified 106 EBV-seronegative individuals, randomly selected a control group EBV-seropositive donors from donor pool. A larger than expected proportion subjects...
Abstract Spleen tyrosine kinase (Syk) is an essential player in immune signaling through its ability to couple multiple classes of membrane immunoreceptors intracellular pathways. Ligand binding leads the recruitment Syk a phosphorylated cytoplasmic region receptors called ITAM. binds ITAM with high‐affinity (nanomolar K d ) via tandem pair SH2 domains. The affinity between and allosterically regulated by phosphorylation at Y130 linker connecting domains; when phosphorylated, decreases...
Interleukin-2-inducible T cell kinase (ITK) is critical for signaling and cytotoxicity, control of Epstein-Barr virus (EBV). We identified a patient with novel homozygous missense mutation (D540N) in highly conserved residue the domain ITK who presented EBV-positive lymphomatoid granulomatosis. She was treated interferon chemotherapy her disease went into remission; however, she has persistent elevation EBV DNA blood, low CD4 cells, NK nearly absent iNKT cells. Molecular modeling predicts...