A5011564114- Protein Structure and Dynamics
- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Cellular Mechanics and Interactions
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- SARS-CoV-2 and COVID-19 Research
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- Natural Antidiabetic Agents Studies
- Cell Adhesion Molecules Research
- Magnetism in coordination complexes
- Alzheimer's disease research and treatments
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Glycosylation and Glycoproteins Research
- Metal complexes synthesis and properties
- Electron Spin Resonance Studies
- Genomics and Phylogenetic Studies
- Cancer-related Molecular Pathways
- Gene Regulatory Network Analysis
- Molecular Junctions and Nanostructures
Brunel University of London
2018-2025
Max Planck Institute for Biophysical Chemistry
2012-2021
Indian Institute of Technology Bombay
2015-2020
Tiande (China)
2018
Bioengineering Center
2018
The relationship between protein dynamics and function is essential for understanding biological processes developing effective therapeutics. Functional sites within proteins are critical activities such as substrate binding, catalysis, structural changes. Existing computational methods the predictions of functional residues trained on sequence, structural, experimental data, but they do not explicitly model influence evolution dynamics. This overlooked contribution it known that can...
β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis led to an urgent requirement develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components required as backup against emergence lethal variants. One such target is main protease (Mpro) that plays indispensable role replication. availability over 270 Mpro X-ray structures complex with inhibitors provides...
Glycosylation of secondary metabolites involves plant UDP-dependent glycosyltransferases (UGTs). UGTs have shown promise as catalysts in the synthesis glycosides for medical treatment. However, limited understanding at molecular level due to insufficient biochemical and structural information has hindered potential applications most these UGTs. In absence experimental crystal structures, we employed advanced modeling simulations conjunction with characterization design a workflow study five...
The relationship between protein dynamics and function is essential for understanding biological processes developing effective therapeutics. Functional sites within proteins are critical activities such as substrate binding, catalysis, structural changes. Existing computational methods the predictions of functional residues trained on sequence, experimental data, but they do not explicitly model influence evolution dynamics. This overlooked contribution it known that can fine tune through...
The relationship between protein dynamics and function is essential for understanding biological processes developing effective therapeutics. Functional sites within proteins are critical activities such as substrate binding, catalysis, structural changes. Existing computational methods the predictions of functional residues trained on sequence, experimental data, but they do not explicitly model influence evolution dynamics. This overlooked contribution it known that can fine tune through...
The relationship between protein dynamics and function is essential for understanding biological processes developing effective therapeutics. Functional sites within proteins are critical activities such as substrate binding, catalysis, structural changes. Existing computational methods the predictions of functional residues trained on sequence, structural, experimental data, but they do not explicitly model influence evolution dynamics. This overlooked contribution it known that can...
The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets type 2 diabetic patients that have been associated with β-cell dysfunction and/or death diabetes mellitus (T2DM). Therefore, developing identifying inhibitors hIAPP aggregation pathway compound can mediate disaggregation preformed holds promise as a medical intervention for T2DM management. In current study, anti-amyloidogenic potential Azadirachtin (AZD)-a...
Abstract A copper‐dependent self‐cleaving DNA (DNAzyme or deoyxyribozyme) previously isolated by in vitro selection has been analyzed a combination of Molecular Dynamics (MD) simulations and advanced Electron Paramagnetic Resonance (Electron Spin Resonance) EPR/ESR spectroscopy, providing insights on the structural mechanistic features cleavage reaction. The modeled 46‐nucleotide deoxyribozyme MD forms duplex triplex sub‐structures that flank highly conserved catalytic core. construct can...
Abstract Motivation Computational methods to detect correlated amino acid positions in proteins have become a valuable tool predict intra- and inter-residue protein contacts, structures, effects of mutation on stability function. While there are many tools webservers compute coevolution scoring matrices, is no central repository alignments matrices for large-scale studies pattern detection leveraging biological structural annotations already available UniProt. Results We present Python...
Abstract The aberrant misfolding and self-assembly of human islet amyloid polypeptide (hIAPP)–a hormone that is co-secreted with insulin from pancreatic β-cells–into toxic oligomers, protofibrils fibrils has been observed in type 2 diabetes mellitus (T2DM). formation these insoluble aggregates linked the death dysfunction β-cells. Therefore, hIAPP aggregation identified as a therapeutic target for T2DM management. Several natural products are now being investigated their potential to inhibit...
Polyubiquitination of the target protein by a ubiquitin transferring machinery is key to various cellular processes. E3 ligase Skp1-Cul1-F-box (SCF) one such complex which plays crucial role in substrate recognition and transfer molecule. Previous computational studies have focused on S-phase kinase-associated 2 (Skp2), cullin, RING-finger proteins this complex, but roles adapter Skp1 F-box domain Skp2 not been determined. Using sub-microsecond molecular dynamics simulations full-length...
Legionella pneumophila is a Gram-negative bacterium that able to replicate within broad range of aquatic protozoan hosts. L. also an opportunistic human pathogen can infect macrophages and epithelia in the lung lead Legionnaires' disease. The type II secretion system key virulence factor used promote bacterial growth at low temperatures, regulate biofilm formation, modulate host responses infection, facilitate penetration mucin gels necessary for intracellular during initial stages...
FtsZ monomers assemble to form a dynamic Z-ring at the midcell position in bacteria that coordinates bacterial cell division. Antibacterial agents plumbagin and SB-RA-2001 were found bind inhibit formation bacteria. Docking analysis indicated similar binding regions for these two inhibitors on FtsZ, residue R191 was involved interaction with both compounds. In this work, importance of assembly division analyzed. R191A-FtsZ exhibited significantly poorer polymerization ability. Further,...
Peb4 from Campylobacter jejuni is an intertwined dimeric, periplasmic holdase, which also exhibits peptidyl prolyl cis/trans isomerase (PPIase) activity. gene deletion alters the outer membrane protein profile and impairs cellular adhesion biofilm formation for C. jejuni. Earlier crystallographic study has proposed that PPIase domains are flexible might form a cradle holding substrate these aspects of were explored using sub-microsecond molecular dynamics simulations in solution environment....
Holliday junction (HJ) resolving enzyme RecU is involved in DNA repair and recombination. We have determined the crystal structure of inactive mutant (D88N) from Bacillus subtilis complex with a 12 base palindromic fragment at resolution 3.2 Å. This shows stalk region essential N-terminal (NTR) previously unseen our unbound structure. The flexible nature NTR solution was confirmed using SAXS. Thermofluor studies performed to assess stability arms an HJ indicate that it confers stability....
The relationship between protein dynamics and function is essential for understanding biological processes developing effective therapeutics. Functional sites within proteins are critical activities such as substrate binding, catalysis, structural changes. Existing computational methods the predictions of functional residues trained on sequence, experimental data, but they do not explicitly model influence evolution dynamics. This overlooked contribution it known that can fine tune through...
Molecular dynamics (MD) simulations have become routine tools for the study of protein and function. Thanks to faster GPU-based algorithms, atomistic coarse-grained are being used explore biological functions over microsecond timescale, yielding terabytes data spanning multiple trajectories, thereby extracting relevant conformations without losing important information is often challenging.We present MDSubSampler, a Python library toolkit posteriori subsampling from trajectories. This...
Abstract β-coronaviruses alone have been responsible for three major global outbreaks in the 21 st century. The current crisis has led to an urgent requirement develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components required as back-up against emergence lethal variants. One such target is main protease (M pro ) that plays indispensible role replication. availability over 270 M X-ray structures complex with inhibitors...
Abstract Triosephosphate Isomerase is a glycolytic enzyme catalyzing the interconversion of Dihydroxyacetone phosphate to Glyceraldehyde-3-phosphate. The active site comprised three distinct loops loop-6, loop-7 and loop-8. Based on loop-6 conformation we describe as Open TIM Closed TIM. Various NMR, X-ray crystallography QM/MM simulation techniques have provided glimpses individual events what essentially dynamic process. We studied conformational changes two (loop-6 loop-7) enveloping...
Abstract Selective binding to nucleic acids and, more generally, biopolymers, very often requires at a minimum the presence of specific functionalities and precise spatial arrangement. DNA can fold into defined 3D structures upon metal centers and/or lanthanides. Binding efficiency be boosted by modified nucleosides incorporated sequences. In this work high selectivity towards copper (II) ions, when used in monomeric form, is unexpectedly drastically reduced being covalently attached...