caa a22 4500 605512639 CHVBK 20210128100656.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00894-015-2621-5 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2621-5 Environmental polarity induces conformational transitions in a helical peptide sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular dynamics simulation study [Elektronische Daten] [Harpreet Kaur, Yellamraju Sasidhar] Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant ‘L20' of bacteriophage T4 lysozyme demonstrated a solvent induced α→β transition 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 300K and 1bar (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→β transition 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 Springer-Verlag Berlin Heidelberg, 2015 α→β transition nationallicence Bacteriophage T4 lysozyme nationallicence Salt bridges nationallicence Solvent shielding nationallicence TFE nationallicence Triple stranded β-hairpin nationallicence Kaur Harpreet Department of Chemistry, Indian Institute of Technology Bombay, 400076, Powai, Mumbai, India aut Sasidhar Yellamraju Department of Chemistry, Indian Institute of Technology Bombay, 400076, Powai, Mumbai, India aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-14 1610-2940 21:4<1 2015 21 894 https://doi.org/10.1007/s00894-015-2621-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2621-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kaur Harpreet Department of Chemistry, Indian Institute of Technology Bombay, 400076, Powai, Mumbai, India aut NATIONALLICENCE 700 1- Sasidhar Yellamraju Department of Chemistry, Indian Institute of Technology Bombay, 400076, Powai, Mumbai, India aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-14 1610-2940 21:4<1 2015 21 894