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

Systems-based approach to examine the cytokine responses in primary mouse lung macrophages infected with low pathogenic avian Influenza virus circulating in South East Asia

BACKGROUND:
Influenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year. Zoonotic transmissions of the virus from swine and avian origin have occurred in the past, and can potentially lead to the emgergence of new IAV stains in future pandemics. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response of macrophages infected with avian influenza viruses should provide new therapeutic strategies.

RESULTS:

type: 
Journal Paper
journal: 
BMC Genomics. 2017 May 30;18(1):420. doi: 10.1186/s12864-017-3803-6
pubmed: 
28558796
Url: 
https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3803-6
Impact Factor: 
3.867
Date of acceptance: 
2017-05-05

A novel community driven software for functional enrichment analysis of extracellular vesicles data

Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes.

type: 
Journal Paper
journal: 
Journal of Extracellular Vesicles 2017, Vol. 6, 2017, Issue 1, doi: 10.1080/20013078.2017.1321455
Url: 
http://www.tandfonline.com/doi/abs/10.1080/20013078.2017.1321455
Impact Factor: 
4.259

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

A Study of Nuclei Classification Methods in Histopathological Images

Cancer is a group of diseases involving abnormal cell growth with varying malignancy and extent across different patients. Cytological features like prominent nucleoli, nuclear enlargement, and hyperchromasia are important to the tumor pathologist in assessment of cancer malignancy from tissue biopsies. In a recent study, Yap et al. [21] proposed effective prominent nucleoli detectors in histopathological images and developed different feature generation methods.

type: 
Conference Paper/Poster
journal: 
Proceedings of the 5th KES International Conference on Innovation in Medicine and Healthcare (KES-InMed 2017)
Url: 
https://link.springer.com/chapter/10.1007/978-3-319-59397-5_9

Outbreak of Zika virus infection in Singapore: an epidemiological, entomological, virological, and clinical analysis

BACKGROUND:
An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus infection in Asia.

METHODS:

type: 
Journal Paper
journal: 
The Lancet Infectious Diseases, Vol. 17, No. 8, pg 813-821, Aug 2017, doi: 10.1016/S1473-3099(17)30249-9
pubmed: 
28527892
Url: 
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30249-9/fulltext
Impact Factor: 
19.864

Designing dual inhibitors of Mdm2/MdmX: Unexpected coupling of water with gatekeeper Y100/99

Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet dual inhibitors are challenging to design due to differences in the conformations of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99. Analysis of crystal structures and molecular dynamics (MD) simulations of complexes of Mdm2 and MdmX resulted in the identification of a water molecule with a long residence time that appears to be modulated by the conformation of Y100/99.

type: 
Journal Paper
Url: 
http://onlinelibrary.wiley.com/doi/10.1002/prot.25310/abstract
Impact Factor: 
2.289
Date of acceptance: 
2017-04-17

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
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