Biomolecular Modelling and Design

A yeast two-hybrid system for the screening and characterization of small-molecule inhibitors of protein–protein interactions identifies a novel putative Mdm2-binding site in p53

Background: Protein–protein interactions (PPIs) are fundamental to the growth and survival of cells and serve as excellent targets to develop inhibitors of biological processes such as host-pathogen interactions and cancer cell proliferation. However, isolation of PPI inhibitors is extremely challenging. While several in vitro assays to screen for PPI inhibitors are available, they are often expensive, cumbersome, and require large amounts of purified protein. In contrast, limited in vivo assays are available to screen for small-molecule inhibitors of PPI.

type: 
Journal Paper
journal: 
BMC Biology 2017 15:108, doi: 10.1186/s12915-017-0446-7
Url: 
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0446-7
Impact Factor: 
6.779
Date of acceptance: 
2017-10-19

A New Generation of Arachidonic Acid Analogues as Potential Neurological Agent Targeting Cytosolic Phospholipase A2

Cytosolic phospholipase A2 (cPLA2) is an enzyme that releases arachidonic acid (AA) for the synthesis of eicosanoids and lysophospholipids which play critical roles in the initiation and modulation of oxidative stress and neuroinflammation. In the central nervous system, cPLA2 activation is implicated in the pathogenesis of various neurodegenerative diseases that involves neuroinflammation, thus making it an important pharmacological target. In this paper, a new class of arachidonic acid (AA) analogues was synthesized and evaluated for their ability to inhibit cPLA2.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article no: 13684, 2017, doi:10.1038/s41598-017-13996-8
Url: 
https://www.nature.com/articles/s41598-017-13996-8
Impact Factor: 
4.259
Date of acceptance: 
2017-10-05

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

In Silico and in Vitro Interactions between Short Chain Fatty Acids and Human Histone Deacetylases

Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses.

type: 
Journal Paper
journal: 
Biochemistry, 2017, doi: 10.1021/acs.biochem.7b00508
Impact Factor: 
2.938

A polar SxxS motif drives assembly of the transmembrane domains of Toll-like receptor 4

Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD).

type: 
Journal Paper
journal: 
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2017 Jul 22;1859(10):2086-2095. doi: 10.1016/j.bbamem.2017.07.010
pubmed: 
28739292
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=28739292
Impact Factor: 
3.498
Date of acceptance: 
2017-07-20

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses

Objective To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains.

type: 
Journal Paper
journal: 
Bulletin of the World Health Organization, 2017, Jul 1: 95(7): Pg 517-525i
Url: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487971/
Impact Factor: 
4.939
Date of acceptance: 
2017-01-19

AlloSigMA: Allosteric Signalling and Mutation Analysis server

Motivation: Allostery is an omnipresent mechanism of the function modulation in proteins via either effector binding or mutations in the exosites. Despite the growing number of on-line servers and databases devoted to prediction/classification of allosteric sites and their characteristics, there is a lack of resources for an efficient and quick estimation of the causality and energetics of allosteric communication.

type: 
Journal Paper
journal: 
Bioinformatics, 2017, doi: 10.1093/bioinformatics/btx430
Url: 
https://doi.org/10.1093/bioinformatics/btx430
Impact Factor: 
7.307
Date of acceptance: 
2017-07-29

A Spring-Loaded Mechanism Governs the Clamp-like Dynamics of the Skp Chaperone

The trimeric periplasmic holdase chaperone Skp binds and stabilizes unfolded outer membrane proteins (OMPs) as part of bacterial OMP biogenesis. Skp binds client proteins in its central cavity, thereby reducing its backbone dynamics, but the molecular mechanisms that govern Skp dynamics and adaptation to differently sized clients remains unknown.

type: 
Journal Paper
journal: 
Structure, 2017 Jul 5;25(7):1079-1088.e3. doi: 10.1016/j.str.2017.05.018
pubmed: 
28648612
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28648612
Impact Factor: 
5.618

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

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
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