Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F12%3A33142576" target="_blank" >RIV/61989592:15310/12:33142576 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bpj.2012.03.024" target="_blank" >http://dx.doi.org/10.1016/j.bpj.2012.03.024</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpj.2012.03.024" target="_blank" >10.1016/j.bpj.2012.03.024</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign

Popis výsledku v původním jazyce

We study the folding of the designed hairpin chignolin, using simulations with four different force fields. Interestingly, we find a misfolded, out-of-register, structure comprising 20-50% of the ordered structures with three force fields, but not with afourth. A defining feature of the misfold is that Gly-7 adopts a beta(PR) conformation rather than alpha(L). By reweighting, we show that differences between the force fields can mostly be attributed to differences in glycine properties. Benchmarking against NMR data suggests that the preference for beta(PR) is not a force-field artifact. For chignolin, we show that including the misfold in the ensemble results in back-recalculated NMR observables in slightly better agreement with experiment than parameters calculated from a folded ensemble only. For comparison, we show by NMR and circular dichroism spectroscopy that the G7K mutant of chignolin, in which formation of this misfold is impossible, is well folded with stability similar to

Název v anglickém jazyce

Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign

Popis výsledku anglicky

We study the folding of the designed hairpin chignolin, using simulations with four different force fields. Interestingly, we find a misfolded, out-of-register, structure comprising 20-50% of the ordered structures with three force fields, but not with afourth. A defining feature of the misfold is that Gly-7 adopts a beta(PR) conformation rather than alpha(L). By reweighting, we show that differences between the force fields can mostly be attributed to differences in glycine properties. Benchmarking against NMR data suggests that the preference for beta(PR) is not a force-field artifact. For chignolin, we show that including the misfold in the ensemble results in back-recalculated NMR observables in slightly better agreement with experiment than parameters calculated from a folded ensemble only. For comparison, we show by NMR and circular dichroism spectroscopy that the G7K mutant of chignolin, in which formation of this misfold is impossible, is well folded with stability similar to

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biophysical Journal

ISSN

0006-3495

e-ISSN

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Svazek periodika

102

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1897-1906

Kód UT WoS článku

000303003300024

EID výsledku v databázi Scopus

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