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
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Creator |
SHUKLA, RT
KUMAR, N SASIDHAR, YU |
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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 |
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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.
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Publisher |
WILEY-BLACKWELL
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Date |
2014-10-15T08:17:34Z
2014-10-15T08:17:34Z 2013 |
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Type |
Article
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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 |
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Language |
en
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