Kwoh Chee-Kong

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

Published date : 13 Dec 2017

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
Impact Factor
3.123

Water-Bridge Mediates Recognition of mRNA Cap in eIF4E

Published date : 01 Dec 2016

Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5′ mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which also persist in molecular dynamics simulations. These waters engage an intricate hydrogen-bond network between the cap and protein.

type
Journal Paper
journal
Structure 25, 1–7, January 3, 2017
Impact Factor
5.237

Wetting of non-conserved residue-backbones: A feature indicative of aggregation associated regions of proteins

Published date : 17 Dec 2015

Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using ‘Dehydrons'. ‘Dehydrons' are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved.

type
Journal Paper
journal
Proteins. 2015 Dec 17. doi: 10.1002/prot.24976
Impact Factor
2.627

Efficient and accurate OTU clustering with GPU-based sequence alignment and dynamic dendrogram cutting

Published date : 05 Oct 2015

De novo clustering is a popular technique to perform taxonomic profiling of a microbial community by grouping 16S rRNA amplicon reads into operational taxonomic units (OTUs). In this work, we introduce a new dendrogram-based OTU clustering pipeline called CRiSPy. The key idea used in CRiSPy to improve clustering accuracy is the application of an anomaly detection technique to obtain a dynamic distance cutoff instead of using the de facto value of 97 percent sequence similarity as in most existing OTU

type
Journal Paper
journal
IEEE/ACM Transactions on Computation Biology and Bioinformatics, Vol. 12, No. 5, Sept/Oct 2015
Impact Factor
1.438

Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

Published date : 25 Nov 2011

R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes.

type
Journal Paper
journal
Nucleic Acids Research 2012 January; 40(2): e16, doi: 10.1093/nar/gkr1075
Impact Factor
8.026