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Loop propensity of the sequence YKGQP from staphylococcal nuclease: implications for the folding of nuclease

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Title Loop propensity of the sequence YKGQP from staphylococcal nuclease: implications for the folding of nuclease
 
Creator PATEL, S
SASIDHAR, YU
 
Subject molecular-dynamics simulations
reverse turn conformation
particle mesh ewald
beta-turns
globular-proteins
secondary structure
hydrogen-exchange
escherichia-coli
aqueous-solution
local sequence
turn
loop
peptide
free-energy landscape
staphylococcal nuclease
gromos96
protein folding
 
Description Recently we performed molecular dynamics (MD) simulations on the folding of the hairpin peptide DTVKLMYKGQPMTFR from staphylococcal nuclease in explicit water. We found that the peptide folds into a hairpin conformation with native and nonnative hydrogen-bonding patterns. In all the folding events observed in the folding of the hairpin peptide, loop formation involving the region YKGQP was an important event. In order to trace the origins of the loop propensity of the sequence YKGQP, we performed MD simulations on the sequence starting from extended, polyproline II and native type I' turn conformations for a total simulation length of 300 ns, using the GROMOS96 force field under constant volume and temperature (NVT) conditions. The free-energy landscape of the peptide YKGQP shows minima corresponding to loop conformation with Tyr and Pro side-chain association, turn and extended conformational forms, with modest free-energy barriers separating the minima. To elucidate the role of Gly in facilitating loop formation, we also performed MD simulations of the mutated peptide YKAQP (Gly -> Ala mutation) under similar conditions starting from polyproline II conformation for 100 ns. Two minima corresponding to bend/turn and extended conformations were observed in the free-energy landscape for the peptide YKAQP. The free-energy barrier between the minima in the free-energy landscape of the peptide YKAQP was also modest. Loop conformation is largely sampled by the YKGQP peptide, while extended conformation is largely sampled by the YKAQP peptide. We also explain why the YKGQP sequence samples type II turn conformation in these simulations, whereas the sequence as part of the hairpin peptide DTVKLMYKGQPMTFR samples type I' turn conformation both in the X-ray crystal structure and in our earlier simulations on the folding of the hairpin peptide. We discuss the implications of our results to the folding of the staphylococcal nuclease. Copyright (C) 2007 European Peptide Society and , Ltd.
 
Publisher JOHN WILEY & SONS LTD
 
Date 2011-08-16T22:33:02Z
2011-12-26T12:55:11Z
2011-12-27T05:43:51Z
2011-08-16T22:33:02Z
2011-12-26T12:55:11Z
2011-12-27T05:43:51Z
2007
 
Type Article
 
Identifier JOURNAL OF PEPTIDE SCIENCE, 13(10), 679-692
1075-2617
http://dx.doi.org/10.1002/psc.907
http://dspace.library.iitb.ac.in/xmlui/handle/10054/9647
http://hdl.handle.net/10054/9647
 
Language en