Multiscale Simulation, Modelling, and Design in Biological Chemistry and Biophysics

Editorial Overview : Exploring mechanisms in biology: simulations and experiments come together

type: 
Journal Paper
journal: 
Progress in Biophysics and Molecular Biology, 2017 Sep;128:1-2. doi: 10.1016/j.pbiomolbio.2017.07.005
pubmed: 
28743422
Impact Factor: 
3.227

A polar SxxS motif drives assembly of the transmembrane domains of Toll-like receptor 4

Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD).

type: 
Journal Paper
journal: 
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2017 Jul 22;1859(10):2086-2095. doi: 10.1016/j.bbamem.2017.07.010
pubmed: 
28739292
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=28739292
Impact Factor: 
3.498
Date of acceptance: 
2017-07-20

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses

Objective To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains.

type: 
Journal Paper
journal: 
Bulletin of the World Health Organization, 2017, Jul 1: 95(7): Pg 517-525i
Url: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487971/
Impact Factor: 
4.939
Date of acceptance: 
2017-01-19

A Spring-Loaded Mechanism Governs the Clamp-like Dynamics of the Skp Chaperone

The trimeric periplasmic holdase chaperone Skp binds and stabilizes unfolded outer membrane proteins (OMPs) as part of bacterial OMP biogenesis. Skp binds client proteins in its central cavity, thereby reducing its backbone dynamics, but the molecular mechanisms that govern Skp dynamics and adaptation to differently sized clients remains unknown.

type: 
Journal Paper
journal: 
Structure, 2017 Jul 5;25(7):1079-1088.e3. doi: 10.1016/j.str.2017.05.018
pubmed: 
28648612
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28648612
Impact Factor: 
5.618

Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism

Effective control of endotoxins and bacteria is crucial for normal wound healing. During injury, the key enzyme thrombin is formed, leading to generation of fibrin. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which bind to and form amorphous amyloid-like aggregates with both bacterial lipopolysaccharide (LPS) and gram-negative bacteria.

type: 
Journal Paper
journal: 
Proceedings of the National Academy of Sciences (PNAS), May 4, 2017, doi: 10.1073/pnas.1619609114
pubmed: 
28362432
Url: 
http://www.pnas.org/content/early/2017/05/03/1619609114.abstract
Impact Factor: 
9.661
Date of acceptance: 
2017-05-12

Progress in Molecular Dynamics Simulations of Bacterial Cell Envelopes

Bacteria are protected by complex molecular architectures known as the cell envelope. The cell envelope is composed of regions with distinct chemical compositions and physical properties, namely, membranes and a cell wall. To develop novel antibiotics to combat pathogenic bacteria, molecular level knowledge of the structure, dynamics, and interplay between the chemical components of the cell envelope that surrounds bacterial cells is imperative.

type: 
Journal Paper
journal: 
The Journal of Physical Chemistry Letters, 2017 Jun 1;8(11):2513-2518. doi: 10.1021/acs.jpclett.7b00473
pubmed: 
28467715
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28467715
Impact Factor: 
9.353
Date of acceptance: 
2017-05-03

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections

Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a

type: 
Journal Paper
journal: 
JCI Insight. 2017 Apr 20;2(8). pii: 92428. doi: 10.1172/jci.insight.92428
Url: 
https://insight.jci.org/articles/view/92428
Date of acceptance: 
2017-04-21

Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy Reveals Insights into Membrane-Bound States

Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram-negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed to be anchored by two transmembrane helices, but no information is available for the transmembrane and cytosolic domains. Here we have studied purified oligomeric Wzz complexes using cryoelectron microscopy and resolved the transmembrane regions within a semi-continuous detergent micelle.

type: 
Journal Paper
journal: 
Structure, 2017 May 2;25(5):806-815. e3. doi: 10.1016/j.str.2017.03.017
pubmed: 
28434914
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28434914
Impact Factor: 
5.618

Polar N-terminal Residues Conserved in Type 2 Secretion Pseudopilins Determine Subunit Targeting and Membrane Extraction Steps during Fibre Assembly

Bacterial type 2 secretion systems (T2SS), type 4 pili, and archaeal flagella assemble fibres from initially membrane-embedded pseudopilin and pilin subunits. Fibre subunits are made as precursors with positively charged N-terminal anchors, whose cleavage via the prepilin peptidase, essential for pilin membrane extraction and assembly, is followed by N-methylation of the mature (pseudo)pilin N terminus. The conserved Glu residue at position 5 (E5) of mature (pseudo)pilins is essential for assembly.

type: 
Journal Paper
journal: 
Journal of Molecular Biology, Vol. 429, Issue 11, 2 Jun 2017, Pg 1746-1765
pubmed: 
28427876
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=28427876
Impact Factor: 
4.333

OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment

The envelope of Gram-negative bacteria is highly complex, containing separate outer and inner membranes and an intervening periplasmic space encompassing a peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the outer membrane via globular OmpA-like domains of various proteins. We report atomically detailed simulations of PGN bound to OmpA in three different states, including the isolated C-terminal domain (CTD), the full-length monomer, or the complete full-length dimeric form.

type: 
Journal Paper
journal: 
Structure 2016, Vol. 24, Issue 12, 6 Dec 2016, Pg 2227-2235, doi: 10.1016/j.str.2016.10.009
pubmed: 
27866852
Url: 
http://www.cell.com/structure/abstract/S0969-2126(16)30317-3
Impact Factor: 
5.237
Date of acceptance: 
2016-10-14
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