Record Details

Environmental polarity induces conformational transitions in a helical peptide sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular dynamics simulation study

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Environmental polarity induces conformational transitions in a helical peptide sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular dynamics simulation study
 
Creator KAUR, H
SASIDHAR, YU
 
Subject PROTEIN SECONDARY STRUCTURE
PARTICLE MESH EWALD
AQUEOUS-SOLUTION
STRUCTURAL-CHARACTERIZATION
STAPHYLOCOCCAL NUCLEASE
BETA TRANSITION
TRIFLUOROETHANOL
ALPHA
SOLVENT
NMR
alpha ->beta transition
Bacteriophage T4 lysozyme
Salt bridges
Solvent shielding
TFE
Triple stranded beta-hairpin
 
Description Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant 'L20' of bacteriophage T4 lysozyme demonstrated a solvent induced alpha ->beta transition in a loosely held duplicate helical region, while alpha-helical conformation in the parent region was relatively stabilized by its tertiary interactions with the neighboring residues. The solution NMR of the parent helical sequence, sans its protein context, showed no inherent tendency to adopt a particular secondary structure in pure water but showed alpha-helical propensity in TFE/water and SDS micelles. In this study we investigate the conformational preference of the 'parent' and 'duplicate' sequences, sans the protein context, in pure water and an apolar TFE/water solution. Apolar TFE/water solution is a model for non-polar protein context. We performed MD simulations of the two peptides, in explicit water and 80 % (v/v) TFE/water, using GROMOS 53a6 force field, at 300 K and 1 bar (under NPT conditions). We show that in TFE/water mixture, salt bridges are stabilized by apolar TFE molecules and main chain-main chain hydrogen bonds promote the alpha-helical conformation, particularly in the duplicate peptide. Solvent exposure, in pure water, resulted in an alpha ->beta transition to form a triple stranded beta-sheet structure in the 'duplicate' sequence, with a rare psi-loop topology, while a mixture of turn/bend conformations were adopted by the 'parent' sequence. Thus the differences in conformational preference of the parent and duplicate sequence sans protein context, in pure water and TFE/water, implicate the importance of the environment polarity in dictating the peptide conformation. Mechanism of folding of the observed psi-loop in the duplicate sequence gives insights into folding of this rare beta-sheet topology.
 
Publisher SPRINGER
 
Date 2016-01-14T11:03:14Z
2016-01-14T11:03:14Z
2015
 
Type Article
 
Identifier JOURNAL OF MOLECULAR MODELING, 21(4)
1610-2940
0948-5023
http://dx.doi.org/10.1007/s00894-015-2621-5
http://dspace.library.iitb.ac.in/jspui/handle/100/17427
 
Language en