A Thermodynamic Funnel Drives Bacterial Lipopolysaccharide Transfer in the TLR4 Pathway

Published date : 17 May 2018

The Gram-negative bacterial outer membrane contains lipopolysaccharide, which potently stimulates the mammalian innate immune response. This involves a relay of specialized complexes culminating in transfer of lipopolysaccharide from CD14 to Toll-like receptor 4 (TLR4) and its co-receptor MD-2 on the cell surface, leading to activation of downstream inflammatory responses. In this study we develop computational models to trace the TLR4 cascade in near-atomic detail.

type
Journal Paper
journal
Structure, 26, Pg 1-11, July 3, 2018, doi: 10.1016/j.str.2018.04.007
Impact Factor
4.907

Conformational landscape of the epidermal growth factor receptor kinase reveals a mutant specific allosteric pocket

Published date : 16 May 2018

Activating mutations within the epidermal growth factor receptor (EGFR) kinase domain give rise to several cancers including Non-Small Cell Lung Cancer (NSCLC). Small molecule inhibitors targeted at these mutants have proven to be clinically successful drugs. These molecules are ATP competitive and rapidly result in the emergence of resistance. Recently Jia et al.

type
Journal Paper
journal
Chemical Science, 2018, doi: 10.1039/C8SC01262H
Impact Factor
8.668

Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B, PIG-M, PIG-U, PIG-W, PIG-V, and PIG-Z

Published date : 15 May 2018

Distant homology relationships among proteins with many transmembrane regions (TMs) are difficult to detect as they are clouded by the TMs’ hydrophobic compositional bias and mutational divergence in connecting loops. In the case of several GPI lipid anchor biosynthesis pathway components, the hidden evolutionary signal can be revealed with dissectHMMER, a sequence similarity search tool focusing on fold-critical, high complexity sequence segments.

type
Journal Paper
journal
Cell Cycle, Vol 17, 2018, Issue 7, doi: 10.1080/15384101.2018.1456294
Impact Factor
3.304

Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy

Published date : 11 May 2018

Background
Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients.

type
Journal Paper
journal
BMC Cancer (2018), 18:555, doi: 10.1186/s12885-018-4471-x
Impact Factor
3.288

Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Published date : 11 May 2018

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action.

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2018, doi: 10.1016/j.bbamem.2018.05.004
Impact Factor
3.498

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. – An in vitro and in vivo study

Published date : 08 May 2018

Background
Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions.

Purpose
The aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4.

type
Journal Paper
journal
Phytomedicine, Vol. 48, 15 Sept 2018, Pg 32-42, doi: 10.1016/j.phymed.2018.05.004
Impact Factor
3.610

Three-dimensional computational model of multiphase flow driven by a bed of active cilia

Published date : 02 May 2018

Micro-scale physiological fluid propulsion is often accomplished with arrays of beating cilia. It is well-known that cilia can spontaneously coordinate their beat patterns to form metachronal waves. While it is generally agreed upon that metachronal waves arise largely due to hydrodynamic coupling, their effects on fluid propulsion are not thoroughly explored. There are presently complex, nonlinear models where cilia motion mimics their internal mechanisms; however these models are often computationally challenging and expensive to perform.

type
Journal Paper
journal
Computers & Fluids, Vol. 170, 15 Jul 2018, Pg 222-235, doi: 10.1016/j.compfluid.2018.05.001
Impact Factor
2.221

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence

Published date : 28 Apr 2018

Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity.

type
Journal Paper
journal
Archives of Toxicology, April 2018, doi: 10.1007/s00204-018-2213-0
Impact Factor
5.901

Comparison of Charge Derivation Methods Applied to Amino Acid Parametrization

Published date : 27 Apr 2018

When using non-natural amino acids in computational simulations of proteins, it is necessary to ensure appropriate parameterization of the new amino acids toward the creation of appropriate input files. In particular, the charges on the atoms may have to be derived de novo and ad hoc for the new species. As there are many variables in the charge derivation process, an investigation was devised to compare different approaches and determine their effect on simulations. This was done with the purpose to identify the methods which produced results compatible with the existing parameters.

type
Journal Paper
journal
ACS Omega 2018, 3, Pg 4664-4673, doi: 10.1021/acsomega.8b00438

Human mesenchymal stem cell basal membrane bending on gratings is dependent on both grating width and curvature

Published date : 24 Apr 2018

The topography of the extracellular substrate provides physical cues to elicit specific downstream biophysical and biochemical effects in cells. An example of such a topographical substrate is periodic gratings, where the dimensions of the periodic gratings influence cell morphology and directs cell differentiation.

type
Journal Paper
journal
Scintific Reports 8, No. 6444, 2018, doi: 10.1038/s41598-018-24123-6
Impact Factor
4.122