VERMA Chandra

Editorial Overview : Exploring mechanisms in biology: simulations and experiments come together

type: 
Journal Paper
journal: 
Progress in Biophysics and Molecular Biology, 2017 Sep;128:1-2. doi: 10.1016/j.pbiomolbio.2017.07.005
pubmed: 
28743422
Impact Factor: 
3.227

The interfacial character of antibody paratopes: analysis of antibody-antigen structures

In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen.

type: 
Journal Paper
journal: 
Bioinformatics, 2017, doi: 10.1093/bioinformatics/btx389
Url: 
https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btx389
Impact Factor: 
7.307
Date of acceptance: 
2017-06-11

Targeting YAP/TAZ-TEAD protein-protein interactions using fragment-based and computational modeling approaches

The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment.

type: 
Journal Paper
journal: 
PLoS One, 2017 Jun 1, doi: org/10.1371/journal.pone.0178381
Url: 
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178381
Impact Factor: 
2.8
Date of acceptance: 
2017-05-11

Role of N-glycosylation in EGFR ectodomain ligand binding

The epidermal growth factor receptor (EGFR) is a tyrosine kinase protein, overexpressed in several cancers. The extracellular domain of EGFR is known to be heavily glycosylated. Growth factor (mostly epidermal growth factor or EGF) binding activates EGFR. This occurs by inducing the transition from the autoinhibited tethered conformation to an extended conformation of the monomeric form of EGFR and by stabilizing the flexible preformed dimer.

type: 
Journal Paper
journal: 
Proteins: Structure, Function, and Bioinformatics, Vol. 85, Issue 8, Aug 2017, Pg. 1529-1549, doi: 10.1002/prot.25314
pubmed: 
28486782
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28486782
Impact Factor: 
2.289

Modeling the Structure of Keratin 1 and 10 Terminal Domains and their Misassembly in Keratoderma

The terminal domains of suprabasal keratins of the skin epithelium are very resistant to evidence-based structural analysis because of their inherent flexibility and lack of predictable structure. We present a model for the structure and interactions of the head and tail domains of epidermal keratins 1 and 10, based on all-atom 3D simulations of keratin primary amino acid sequences, and tyrosine phosphorylation predictions, extracted from published databases.

type: 
Journal Paper
journal: 
Journal of Investigative Dermatology, 2017 May 16. pii: S0022-202X(17)31522-1. doi: 10.1016/j.jid.2017.03.038
pubmed: 
28526297
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=28526297
Impact Factor: 
6.287
Date of acceptance: 
2017-03-20

Hydration effects on the efficacy of the Epidermal growth factor receptor kinase inhibitor afatinib

Small molecules targeting the EGFR tyrosine kinase domain have been used with some success at treating patients with non-small cell lung cancer driven by activating mutations in the kinase domain. The initial class of inhibitors displaced ATP noncovalently but were rendered ineffective due to the development of resistance mutations in the kinase domain. These were overcome by the development of covalent inhibitors such as afatinib which also bind in the ATP pocket.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article no: 1540 (2017), doi:10.1038/s41598-017-01491-z
Url: 
https://www.nature.com/articles/s41598-017-01491-z?WT.feed_name=subjects_biophysics
Impact Factor: 
4.259
Date of acceptance: 
2017-03-28

Regulation of Transcriptional Activators by DNA-Binding Domain Ubiquitination

Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin.

type: 
Journal Paper
journal: 
Cell Death and Differentiation 2017 May;24(5):903-916. doi: 10.1038/cdd.2017.42
pubmed: 
, PMID: 28362432
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28362432
Impact Factor: 
8.218
Date of acceptance: 
2017-02-16

Molecular Environment Modulates Conformational Differences between Crystal and Solution States of Human beta-defensin 2

Human β-defensin 2 is a cysteine-rich antimicrobial peptide. In the crystal state, the N-terminal segment (residues 1−11) exhibits a helical conformation. However, a truncated form, with four amino acids removed from the N-terminus, adopts nonhelical conformations in solution, as shown by NMR. To explore the molecular origins of these different conformations, we performed Hamiltonian replica exchange molecular dynamics simulations of the peptide in solution and in the crystal state.

type: 
Journal Paper
journal: 
Journal of Physical Chemistry Part B, 2017, doi : 10.1021/acs.jpcb.7b00083
Impact Factor: 
3.177
Date of acceptance: 
2017-03-15

Hierarchical Assembly of Tough Bioelastomeric Egg Capsules is Mediated by a Bundling Protein

Marine snail egg capsules are shock-absorbing bioelastomers made from precursor "egg case proteins" (ECPs) that initially lack long-range order. During capsule formation, these proteins self-assemble into coiled-coil filaments that subsequently align into microscopic layers, a multiscale process which is crucial to the capsules' shock-absorbing properties.

type: 
Journal Paper
journal: 
Biomacromolecules, 2017, 18 (3), pg 931-942, doi: 10.1021/acs.biomac.6b01810
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28196415
Impact Factor: 
5.583
Date of acceptance: 
2017-03-16

Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design

Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress.

type: 
Journal Paper
journal: 
Frontiers in Neuroscience, Feb 2017, Vol. 11, Article 73, doi: 10.3389/fnins.2017.00073
Url: 
http://journal.frontiersin.org/article/10.3389/fnins.2017.00073/full
Impact Factor: 
3.398
Date of acceptance: 
2017-01-31
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