Folding cooperativity in a three-stranded β-sheet model

JOURNAL OF MOLECULAR BIOLOGY

卷:352

Article

Roe, DR ; Hornak, V ; Simmerling, C

关键词: beta-sheet;    beta-hairpin;    protein folding;    molecular dynamics;    folding cooperativity;   

DOI  :  10.1016/j.jmb.2005.07.036

来源: Elsevier

【 摘 要 】

The thermodynamic behavior of a previously designed three-stranded beta-sheet was studied via several microseconds of standard and replica exchange molecular dynamics simulations. The system is shown to populate at least four thermodynamic minima, including two partially folded states in which only a single hairpin is formed. Simulated melting curves show different profiles for the C and N-terminal hairpins, consistent with differences in secondary structure content in published NMR and CD/FTIR measurements, which probed different regions of the chain. Individual beta-hairpins that comprise the three-stranded beta-sheet are observed to form cooperatively. Partial folding cooperativity between the component hairpins is observed, and good agreement between calculated and experimental values quantifying this cooperativity is obtained when similar analysis techniques are used. However, the structural detail in the ensemble of conformations sampled in the simulations permits a more direct analysis of this cooperativity than has been performed on the basis of experimental data. The results indicate the actual folding cooperativity perpendicular to strand direction is significantly larger than the lower bound obtained previously. (c) 2005 Elsevier Ltd. All rights reserved.

【 授权许可】

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