scholarly journals All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer

ACS Omega ◽  
2021 ◽  
Vol 6 (17) ◽  
pp. 11458-11465
Author(s):  
Hayato Itaya ◽  
Kota Kasahara ◽  
Qilin Xie ◽  
Yoshiaki Yano ◽  
Katsumi Matsuzaki ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayer ◽  
Molecular Mechanisms ◽  
Model Peptide ◽  
Peptide Dimerization

scholarly journals Ketoamide Resistance and Hepatitis C Virus Fitness in Val55 Variants of the NS3 Serine Protease

2012 ◽  
Vol 56 (4) ◽  
pp. 1907-1915 ◽  
Author(s):  
Christoph Welsch ◽  
Sabine Schweizer ◽  
Tetsuro Shimakami ◽  
Francisco S. Domingues ◽  
Seungtaek Kim ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Rna Replication ◽  
Viral Fitness ◽  
Dynamics Simulation ◽  
Structural Flexibility ◽  
Residue Interaction

ABSTRACTDrug-resistant viral variants are a major issue in the use of direct-acting antiviral agents in chronic hepatitis C. Ketoamides are potent inhibitors of the NS3 protease, with V55A identified as mutation associated with resistance to boceprevir. Underlying molecular mechanisms are only partially understood. We applied a comprehensive sequence analysis to characterize the natural variability at Val55 within dominant worldwide patient strains. A residue-interaction network and molecular dynamics simulation were applied to identify mechanisms for ketoamide resistance and viral fitness in Val55 variants. An infectious H77S.3 cell culture system was used for variant phenotype characterization. We measured antiviral 50% effective concentration (EC50) and fold changes, as well as RNA replication and infectious virus yields from viral RNAs containing variants. Val55 was found highly conserved throughout all hepatitis C virus (HCV) genotypes. The conservative V55A and V55I variants were identified from HCV genotype 1a strains with no variants in genotype 1b. Topology measures from a residue-interaction network of the protease structure suggest a potential Val55 key role for modulation of molecular changes in the protease ligand-binding site. Molecular dynamics showed variants with constricted binding pockets and a loss of H-bonded interactions upon boceprevir binding to the variant proteases. These effects might explain low-level boceprevir resistance in the V55A variant, as well as the Val55 variant, reduced RNA replication capacity. Higher structural flexibility was found in the wild-type protease, whereas variants showed lower flexibility. Reduced structural flexibility could impact the Val55 variant's ability to adapt for NS3 domain-domain interaction and might explain the virus yield drop observed in variant strains.

scholarly journals An Alamethicin Channel in a Lipid Bilayer: Molecular Dynamics Simulations

1999 ◽  
Vol 76 (4) ◽  
pp. 1757-1769 ◽  
Author(s):  
D. Peter Tieleman ◽  
Herman J.C. Berendsen ◽  
Mark S.P. Sansom
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayer ◽  
Dynamics Simulations

A multi-scale molecular dynamics simulation of PMAL facilitated delivery of siRNA

RSC Advances ◽  
2015 ◽  
Vol 5 (83) ◽  
pp. 68227-68233 ◽  
Author(s):  
Jipeng Li ◽  
Yiyun Ouyang ◽  
Xian Kong ◽  
Jingying Zhu ◽  
Diannan Lu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Lipid Bilayer ◽  
Dynamics Simulation ◽  
Lipid Bilayer Membranes ◽  
Bilayer Membranes ◽  
Multi Scale

PMAL as a novel carrier for the delivery of siRNA into lipid bilayer membranes.

Molecular dynamics studies of lipid bilayer with gramicidin A: Effects of gramicidin a on membrane structure and hydrophobic match

2011 ◽  
Vol 112 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Hiroaki Saito ◽  
Taku Mizukami ◽  
Shuhei Kawamoto ◽  
Takeshi Miyakawa ◽  
Masashi Iwayama ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayer ◽  
Membrane Structure ◽  
Gramicidin A
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