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

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• 作者：Harpreet Kaur ; Yellamraju U. Sasidhar
• 关键词：α→οtransition ; Bacteriophage T4 lysozyme ; Salt bridges ; Solvent shielding ; TFE ; Triple stranded β ; hairpin
• 刊名：Journal of Molecular Modeling
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：21
• 期：4
• 全文大小：3,427 KB
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• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023

文摘

Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant ‘L20-of bacteriophage T4 lysozyme demonstrated a solvent induced α→οtransition in a loosely held duplicate helical region, while α-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 α-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 α-helical conformation, particularly in the duplicate peptide. Solvent exposure, in pure water, resulted in an α→οtransition to form a triple stranded β-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 β-sheet topology. Graphical Abstract An apolar environment provided by TFE protects the salt bridges and main chain-main chain hydrogen bonds from solvent exposure in the duplicate peptide sequence, from bacteriophage T4 lysozyme mutant 'L20'. This results in retention of residual a-helical propensity (top). Exposure to pure water results in an a?b transition resulting in a triple stranded b-hairpin (bottom). Differences in conformational preference of the peptide sequence upon change in solvent conditions implicate the importance of the environmental polarity in dictating the peptide conformation