A5042006839- Enzyme Structure and Function
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Cell death mechanisms and regulation
- Bioinformatics and Genomic Networks
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- 14-3-3 protein interactions
- Lipid Membrane Structure and Behavior
- Mass Spectrometry Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Synthesis and Characterization of Heterocyclic Compounds
- IoT-based Smart Home Systems
- Pancreatic function and diabetes
- Robotic Path Planning Algorithms
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- Chemical Synthesis and Analysis
- Cancer-related Molecular Pathways
- Autophagy in Disease and Therapy
- Field-Flow Fractionation Techniques
- Microbial Natural Products and Biosynthesis
- Protein Interaction Studies and Fluorescence Analysis
Fox Chase Cancer Center
2014-2021
Indian Institute of Technology Kanpur
2012-2017
Targeting protein kinases is an important strategy for intervention in cancer. Inhibitors are directed at the active conformation or a variety of inactive conformations. While attempts have been made to classify these conformations, structurally rigorous catalog states has not achieved. The kinase activation loop crucial catalysis and begins with conserved DFGmotif. This motif observed two major classes DFGin-a set conformations where Phe residue contact C-helix N-terminal lobe-and DFGout-an...
Structural coverage of the human kinome has been steadily increasing over time. The structures provide valuable insights into molecular basis kinase function and also a foundation for understanding mechanisms inhibitors. There are large number in PDB which Asp Phe DFG motif on activation loop swap positions, resulting formation new allosteric pocket. We refer to these as "classical DFG-out" conformations order distinguish them from that have referred DFG-out literature but do not fully...
Studies on the structures and functions of individual kinases have been used to understand biological properties other that do not yet experimental structures. The key factor in accurate inference by homology is an sequence alignment. We present a parsimonious, structure-based multiple alignment (MSA) 497 human protein kinase domains excluding atypical kinases. arranged 17 blocks conserved regions unaligned between contain insertions varying lengths only subset aligned well-conserved...
Abstract The active form of kinases is shared across different family members, as are several commonly observed inactive forms. We previously performed a clustering the conformation activation loop all protein kinase structures in Protein Data Bank (PDB) into eight classes based on dihedral angles that place Phe side chain DFG motif at N-terminus loop. Our clusters strongly associated with placement loop, C-helix, and other structural elements kinases. present Kincore, web resource providing...
The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the (PDB). goal of PDBe-KB place macromolecular structure their biological context by developing standardised exchange formats integrating partner into a knowledge graph that can provide valuable insights. Since we described 2019, there have been significant...
CASP11 (the 11th Meeting on the Critical Assessment of Protein Structure Prediction) ran a blind experiment in refinement protein structure predictions, fourth such since CASP8. As with previous experiments, predictors were provided one starting from server models each selected set template-based modeling targets and asked to refine coordinates toward native. We assessed refined structures Z-scores standard CASP measures, which compare model-target similarities all predictors. Furthermore,...
We present the assessment of predictions submitted in template-based modeling (TBM) category CASP11 (Critical Assessment Protein Structure Prediction). Model quality was judged on basis global and local measures accuracy all atoms including side chains. The top groups 39 human-server targets based model 1 were LEER, Zhang, LEE, MULTICOM, Zhang-Server. 81 by server Zhang-Server, nns, BAKER-ROSETTASERVER, QUARK, myprotein-me. In CASP11, best models for most equal to or better than template...
The anti-apoptotic protein Bfl-1, also known as A1, belongs to the Bcl-2 family of proteins and interacts with pro-apoptotic counterparts regulate programmed cell death. As demonstrated for other proteins, Bfl-1/A1 has been shown be overexpressed in various human cancers hence they are attractive targets anticancer drugs. Peptides derived from BH3 region have elicit similar biological response that parent proteins. peptides different wide range affinities Bfl-1/A1. Experimentally determined...
Bcl-XL is a member of Bcl-2 family proteins involved in the regulation intrinsic pathway apoptosis. Its overexpression many human cancers makes it an important target for anti-cancer drugs. interacts with BH3 domain several pro-apoptotic partners. This helical bundle protein has pronounced hydrophobic groove which acts as binding region domains. Eight independent molecular dynamics simulations apo/holo forms were carried out to investigate behavior solvent-exposed groove. The used either...
In CASP11, the organizers sought to bring biological inferences from predicted structures fore. To accomplish this, we assessed models for their ability perform quantifiable tasks related function. First, 10 targets that were probable homodimers, measured accuracy of docking into homodimers as a function GDT-TS monomers, which produced characteristic L-shaped plots. At low GDT-TS, none could be docked correctly homodimers. Above ∼60%, some formed correct in one largest clusters, while many...
Abstract Studies on the structures and functions of individual kinases have been used to understand biological properties other that do not yet experimental structures. The key factor in accurate inference by homology is an sequence alignment. We present a parsimonious, structure-based multiple alignment (MSA) 497 human protein kinase domains excluding atypical kinases, even those with related but somewhat different folds. arranged 17 blocks conserved regions unaligned between contain...
Proteins belonging to Bcl-2 family regulate intrinsic cell death pathway. Although mammalian antiapoptotic members interact with multiple proapoptotic proteins, the Caenorhabditis elegans homolog CED-9 is known have only two partners. The BH3-motif of proteins bind hydrophobic groove prosurvival formed by helical fold. also CED-4, a human activator Apaf1. We performed molecular dynamics simulations in forms and compared results those counterparts Bcl-XL, Bcl-w, Bcl-2. Our studies demonstrate...
ABSTRACT The active form of kinases is shared across different family members, as are several commonly observed inactive forms. We previously performed a clustering the conformation activation loop all protein kinase structures in Protein Data Bank (PDB) into 8 classes based on dihedral angles that place Phe side chain DFG motif at N-terminus loop. Our clusters strongly associated with placement loop, C-helix, and other structural elements kinases. present Kincore, web resource providing...
Abstract Targeting protein kinases is an important strategy for intervention in cancer. Inhibitors are directed at the active conformation or a variety of inactive conformations. While attempts have been made to classify these conformations, structurally rigorous catalogue states has not achieved. The kinase activation loop crucial catalysis and begins with conserved DFGmotif (Asp-Phe-Gly). This motif observed two major classes DFGin - set conformations where Phe residue contact C-helix...