Toward Comprehensive Allosteric Control over Protein Activity

Published date : 28 Feb 2019

Universality of allosteric signaling in proteins, molecular machines, and receptors complemented by the great advantages of prospected allosteric drugs in the highly specific, non-competitive, and modulatory nature of their actions calls for deeper theoretical understanding of allosteric communication. We present a computational model that makes it possible to tackle the problem of modulating the energetics of protein allosteric communication.

type
Journal Paper
journal
Structure 27, Pg 1-13, May 7, 2019, doi: 10.1016/j.str.2019.01.1016
Impact Factor
4.907

Discovering Putative Protein Targets of Small Molecules: A Study of the p53 Activator Nutlin

Published date : 22 Feb 2019

Small molecule drugs bind to a pocket in disease causing target proteins based on complementarity in shape and physicochemical properties. There is a likelihood that other proteins could have binding sites that are structurally similar to the target protein. Binding to these other proteins could alter their activities leading to off target effects of the drug. One such small molecule drug Nutlin binds the protein MDM2, which is upregulated in several types of cancer and is a negative regulator of the tumor suppressor protein p53.

type
Journal Paper
journal
Journal of Chemical Information and Modeling, 2019. 59, (4) Pg. 1529-1546, doi: 10.1021/acs.jcim.8b00762
Impact Factor
3.804

Superresolution microscopy reveals distinct localisation of full length IRSp53 and its I-BAR domain protein within filopodia

Published date : 21 Feb 2019

Superresolution microscopy offers the advantage of imaging biological structures within cells at the nano-scale. Here we apply two superresolution microscopy techniques, specifically 3D structured illumination microscopy (3D-SIM) and direct stochastic optical reconstruction microscopy (dSTORM), a type of single molecule localisation microscopy, to localise IRSp53 protein and its I-BAR domain in relation to F-actin within filopodia. IRSp53 generates dynamic (extending and retracting) filopodia 300 nm wide with a distinct gap between IRSp53 and F-actin.

type
Journal Paper
journal
Scientific Reports 9, Article no: 2524(2019). doi: 10.1038/s41598-019-38851-w
Impact Factor
4.122

Application Notes on APD Areametric App: Automated area quantification for both Android and iOS

Published date : 08 Feb 2019

Area measurements have a wide range of uses from the monitoring of skin features in healthcare, celestial bodies in astronomy, to determining furniture sizes in everyday indoor uses. Current measurement methods utilize some form of measuring tool and unless performed by skilled and trained professionals, human errors leading to inaccurate measurements can often arise. This is especially so for irregularly shaped objects with complex dimensions.

type
Journal Paper
journal
APD Trove 2019, Vol: 2;1, doi: 10.30943/2019/08022019

Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting

Published date : 06 Feb 2019

The multi-faceted role of the transcription factor p53 is key to numerous biological processes, including the suppression of tumours. The availability since the 1990s of a richness of biophysical data aimed at understanding its structure-function relationships has enabled the application of a variety of atomistic computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53.

type
Journal Paper
journal
Journal of Molecular Cell Biology, 2019, 11(4), Pg 306-316, doi: 10.1093/jmcb/mjz009
Impact Factor
5.595

A Review of Apps for Programming: programming languages and making apps with apps

Published date : 26 Jan 2019

With the latest technologies enabling smartphones to work like mini computers, there are now numerous opportunities to use smartphones for the development of mobile apps. Given the multiple Operating Systems (OS) available, there is a significant demand for apps for the various platforms. To meet this demand, some apps exist to impart the necessary knowledge to make apps, while others make the programming of apps possible on these devices. Surveying both the Google Play and Apple App stores, there are a plethora of such programming apps, classified based on the various languages.

type
Journal Paper
journal
Scientific Phone Apps and Mobile Devices (2019) 5:1, doi:10.30943/2019/25012019

Kinetic and thermodynamic effects of phosphorylation on p53 binding to MDM2

Published date : 24 Jan 2019

p53 is frequently mutated in human cancers. Its levels are tightly regulated by the E3 ubiquitin ligase MDM2. The complex between MDM2 and p53 is largely formed by the interaction between the N-terminal domain of MDM2 and the N-terminal transactivation (TA) domain of p53 (residues 15-29). We investigated the kinetic and thermodynamic basis of the MDM2/p53 interaction by using wild-type and mutant variants of the TA domain. We focus on the effects of phosphorylation at positions Thr18 and Ser20 including their substitution with phosphomimetics.

type
Journal Paper
journal
Scientific Reports 9, Article no: 693 (2019). doi: 10.1038/s41598-018-36589-5
Impact Factor
4.122

Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations

Published date : 24 Jan 2019

Dengue is a mosquito-borne virus with dire health and economic impacts. Dengue is responsible for an estimated 390 million infections per year, with dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also in strains of this serotype that temperature-dependent large-scale morphological changes, termed “breathing,” have been observed. Although the structure of these morphologies has been solved to 3.5-Å resolution, the dynamics of the viral envelope are unknown.

type
Journal Paper
journal
Structure, 27, Pg 1-13, 2019, doi: 10.1016/j.str.2018.12.006
Impact Factor
4.907

AllerCatPro - Prediction of protein allergenicity potential from the protein sequence

Published date : 18 Jan 2019

MOTIVATION:
Due to the risk of inducing an immediate type I (IgE-mediated) allergic response, proteins intended for use in consumer products must be investigated for their allergenic potential before introduction into the marketplace. The FAO/WHO guidelines for computational assessment of allergenic potential of proteins based on short peptide hits and linear sequence window identity thresholds misclassify many proteins as allergens.

type
Journal Paper
journal
Bioinformatics. 2019 Jan 18. doi: 10.1093/bioinformatics/btz029
Impact Factor
5.481

Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue

Published date : 17 Jan 2019

Beiging of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of metabolic diseases through norepinephrine (NE)-mediated signaling pathways. Although previous studies report NE clearance mechanisms via SLC6A2 on sympathetic neurons or proinflammatory macrophages in adipose tissues (ATs), the low catecholamine clearance capacity of SLC6A2 may limit the cleaning efficiency.

type
Journal Paper
journal
PLOS Biology, January 17 2019, doi: 10.1371/journal.pbio.2006571
Impact Factor
9.163