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Molecular dynamics simulations of certain mutant peptide models from staphylococcal nuclease reveal that initial hydrophobic collapse associated with turn propensity drives -hairpin folding

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Title Molecular dynamics simulations of certain mutant peptide models from staphylococcal nuclease reveal that initial hydrophobic collapse associated with turn propensity drives -hairpin folding
 
Creator SHUKLA, RT
KUMAR, N
SASIDHAR, YU
 
Subject -turn
-hairpin
glycine mutants
hydrophobic collapse
molecular dynamics simulation
protein folding
ACID-BINDING PROTEIN
PARTICLE MESH EWALD
BETA-HAIRPIN
LOOP PROPENSITY
SECONDARY STRUCTURE
HYDROGEN-EXCHANGE
TRANSITION-STATE
WW DOMAIN
MECHANISM
INTERPLAY
 
Description An important nucleation event during the folding of staphylococcal nuclease involves the formation of a -hairpin by the sequence (21)DTVKLMYKGQPMTFR(35). Earlier studies show that the turn sequence YKGQP' has an important role in the folding of this -hairpin. To understand the active or passive nature of the turn sequence YKGQP' in the folding of the aforementioned -hairpin sequence, we studied glycine mutant peptides Ac-(2)DTVKLMYGGQPMTFR(16)-NMe (K9G:15), Ac-(2)DTVKLMYKGGPMTFR(16)-NMe (Q11G:15), Ac-(2)DTVKLMYGGGPMTFR(16)-NMe (K9G/Q11G:15), and Ac-(2)DTVKLMGGGGGMTFR(16)-NMe (penta-G:15) by using molecular dynamics simulations, starting with two different unfolded states, polyproline II and extended conformational forms. Further, 5mer mutant turn peptides Ac-(2)YGGQP(6)-NMe (K3G:5), Ac-(2)YKGGP(6)-NMe (Q5G:5), Ac-(2)YGGGP(6)-NMe (K3G/Q5G:5), and Ac-(2)GGGGG(6)-NMe (penta-G:5) were also studied individually. Our results show that an initial hydrophobic collapse and loop closure occurs in all 15mer mutants, but only K9G:15 mutant forms a stable native-like -hairpin. In the other 15mer mutants, the hydrophobic collapsed state would not proceed to -hairpin formation. Of the different simulations performed for the penta-G:15 mutant, in only one simulation a nonnative -hairpin conformation is sampled with highly flexible loop region ((8)GGGGG(12)), which has no specific conformational preference as a 5mer. While the sequence YGGQP' in the K3G:5 simulation shows relatively higher -turn propensity, the presence of this sequence in K9G:15 peptide seems to be driving the -hairpin formation. Thus, these results seem to suggest that for the formation of a stable-hairpin, the initial hydrophobic collapse is to be assisted by a turn propensity. Initial hydrophobic collapse alone is not sufficient to guide -hairpin formation. Copyright (c) 2013 European Peptide Society and John Wiley & Sons, Ltd.
 
Publisher WILEY-BLACKWELL
 
Date 2014-10-15T08:17:34Z
2014-10-15T08:17:34Z
2013
 
Type Article
 
Identifier JOURNAL OF PEPTIDE SCIENCE, 19(8)516-527
http://dx.doi.org/10.1002/psc.2530
http://dspace.library.iitb.ac.in/jspui/handle/100/14662
 
Language en