A computational study for rational HIV-1 non-nucleoside Reverse Transcriptase inhibitor selection and the discovery of novel allosteric pockets for inhibitor design

HIV drug resistant mutations that render the current Highly Active Anti-Retroviral Therapy cocktail drugs ineffective are increasingly reported. To study the mechanisms of these mutations in conferring drug resistance, we computationally analyzed fourteen Reverse Transcriptase (RT) structures of HIV-1 on the following parameters: drug-binding pocket volume, allosteric effects caused by the mutations, and structural thermal stability.

type: 
Journal Paper
journal: 
Bioscience Reports, 5 Feb 2018, doi: 10.1042/BSR20171113
Url: 
http://www.bioscirep.org/content/early/2018/02/05/BSR20171113
Impact Factor: 
2.906

Identification of a biosynthetic gene cluster for the polyene macrolactam sceliphrolactam in a Streptomyces strain isolated from mangrove sediment

Streptomyces are a genus of Actinobacteria capable of producing structurally diverse natural products. Here we report the isolation and characterization of a biosynthetically talented Streptomyces (Streptomyces sp. SD85) from tropical mangrove sediments. Whole-genome sequencing revealed that Streptomyces sp. SD85 harbors at least 52 biosynthetic gene clusters (BGCs), which constitute 21.2% of the 8.6-Mb genome. When cultivated under lab conditions, Streptomyces sp. SD85 produces sceliphrolactam, a 26-membered polyene macrolactam with unknown biosynthetic origin.

type: 
Journal Paper
journal: 
Scientific Reports 8, Article no. 1594 (2018), doi:10.1038/s41598-018-20018-8
Url: 
https://www.nature.com/articles/s41598-018-20018-8
Impact Factor: 
4.259
Date of acceptance: 
2017-10-12

The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab recombinant models: Impact on antibody production and antigen-binding

Current therapeutic antibodies such as Trastuzumab, are typically of the blood circulatory IgG1 class (Cκ/ CHγ1). Due to the binding to Her2 also present on normal cell surfaces, side effects such as cardiac failure can sometimes be associated with such targeted therapy. Using antibody isotype swapping, it may be possible to reduce systemic circulation through increased tissue localization, thereby minimising unwanted side effects. However, the effects of such modifications have yet to be fully characterized, particularly with regards to their biophysical properties in antigen binding.

type: 
Journal Paper
journal: 
Scientific Reports 8, Article no 718, 2018, doi:10.1038/s41598-017-18892-9
Url: 
https://www.nature.com/articles/s41598-017-18892-9?WT.feed_name=subjects_immunotherapy
Impact Factor: 
4.259
Date of acceptance: 
2017-12-19

Cytoplasmic polyadenylation-mediated translational control of maternal mRNAs directs maternal-to-zygotic transition

In the earliest stages of animal development following fertilization, maternally deposited mRNAs direct biological processes to the point of zygotic genome activation (ZGA). These maternal mRNAs undergo cytoplasmic polyadenylation (CPA), suggesting translational control of their activation. To elucidate the biological role of CPA during embryogenesis, we performed genome-wide polysome profiling at several stages of zebrafish development. Our analysis revealed a correlation between CPA and polysome-association dynamics, demonstrating a coupling of translation to the CPA of maternal mRNAs.

type: 
Journal Paper
journal: 
Development, 8 Jan 2018, Vol 145, Issue 1, doi: 10.1242/dev.159566
pubmed: 
29229769
Url: 
http://dev.biologists.org/content/145/1/dev159566.long
Impact Factor: 
5.843
Date of acceptance: 
2017-11-20

Multivariate Regression with Gross Errors on Manifold-valued Data

We consider the topic of multivariate regression on manifold-valued output, that is, for a multivariate observation, its output response lies on a manifold. Moreover, we propose a new regression model to deal with the presence of grossly corrupted manifold-valued responses, a bottleneck issue commonly encountered in practical scenarios. Our model first takes a correction step on the grossly corrupted responses via geodesic curves on the manifold, then performs multivariate linear regression on the corrected data.

type: 
Journal Paper
journal: 
IEEE Transactions on Pattern Analysis and Machine Intelligence, 2018, doi: 10.1109/TPAMI.2017.2776260
Url: 
http://ieeexplore.ieee.org/document/8246552/
Impact Factor: 
8.329

Role of the N-terminal lid in regulating the interaction of phosphorylated MDMX with p53

Murine double minute 4 protein (MDMX) is crucial for the regulation of the tumor suppressor protein p53. Phosphorylation of the N-terminal domain of MDMX is thought to affect its binding with the transactivation domain of p53, thus playing a role in p53 regulation. In this study, the effects of MDMX phosphorylation on the binding of p53 were investigated using molecular dynamics simulations.

type: 
Journal Paper
journal: 
Oncotarget, 2017, Vol. 8, No. 68, Pg 112825-112840, doi.org/10.18632/oncotarget.22829
Url: 
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=22829
Impact Factor: 
5.168
Date of acceptance: 
2017-10-05

Covariant Conservation Laws and the Spin Hall Effect in Dirac-Rashba Systems

We present a theoretical analysis of two-dimensional Dirac-Rashba systems in the presence of disorder and external perturbations. We unveil a set of exact symmetry relations (Ward identities) that impose strong constraints on the spin dynamics of Dirac fermions subject to proximity-induced interactions. This allows us to demonstrate that an arbitrary dilute concentration of scalar impurities results in the total suppression of nonequilibrium spin Hall currents when only Rashba spin-orbit coupling is present.

type: 
Journal Paper
journal: 
Physical Review Letters, Vol. 119, Issue 24, 14 Dec 2017, doi: 10.1103/PhysRevLett.119.246801
Url: 
https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.119.246801
Impact Factor: 
8.462

Structural analysis of protein tyrosine phosphatase 1B reveals potentially druggable allosteric binding sites

Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable non-active sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologically important in intracellular signal transduction pathways in diverse cell types and tissues. Aberrant PTP1B is associated with obesity, diabetes, cancers, and neurodegenerative disorders.

type: 
Journal Paper
journal: 
Proteins: Structure, Function, and Bioinformatics, 13 Dec 2017, doi: 10.1002/prot.25440
pubmed: 
29235148
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/29235148
Impact Factor: 
2.499
Date of acceptance: 
2017-12-27

Modeling the full length HIV-1 Gag polyprotein reveals the role of its p6 subunit in viral maturation and the effect of non-cleavage site mutations in protease drug resistance

HIV polyprotein Gag is increasingly found to contribute to protease inhibitor resistance. Despite its role in viral maturation and in developing drug resistance, there remain gaps in the knowledge of the role of certain Gag subunits (e.g. p6), and that of non-cleavage mutations in drug resistance. As p6 is flexible, it poses a problem for structural experiments, and is hence often omitted in experimental Gag structural studies.

type: 
Journal Paper
journal: 
Journal of Biomolecular Structure and Dynamics, 2017, Pg 1-40, doi: 10.1080/07391102.2017.1417160
pubmed: 
3.123
Url: 
http://www.tandfonline.com/doi/abs/10.1080/07391102.2017.1417160
Date of acceptance: 
2017-12-05

Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma

Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients.

type: 
Journal Paper
journal: 
Molecular Oncology, 8 Nov 2017, doi: 10.1002/1878-0261.12153
pubmed: 
29117471
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/29117471
Impact Factor: 
5.314
Date of acceptance: 
2017-10-16
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