Exploring the protein G helix free-energy surface by solute tempering metadynamics

被引：61

作者：

Camilloni, Carlo ^{[1
,2
]}

Provasi, Davide ^{[1
,2
]}

Tiana, Guido ^{[1
,2
]}

Broglia, Ricardo A. ^{[1
,2
,3
]}

机构：

[1] Univ Milan, Dept Phys, I-20133 Milan, Italy

[2] Ist Nazl Fis Nucl, Milan Sect, I-20133 Milan, Italy

[3] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark

来源：

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS | 2008年 / 71卷 / 04期

关键词：

free-energy surface; metadynamics; solute tempering; protein G; alpha-helix; pi-helix;

D O I：

10.1002/prot.21852

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The free-energy landscape of the alpha-helix of protein G is studied by means of metadynamics coupled with a solute tempering algorithm. Metadynamics allows to overcome large energy barriers, whereas solute tempering improves the sampling with an affordable computational effort. From the sampled free-energy surface we are able to reproduce a number of experimental observations, such as the fact that the lowest minimum corresponds to a globular conformation displaying some degree of beta-structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a pi-helix state and that the hydrophobic staple motif is present only in the free-energy minimum associated with the helices, and contributes to their stabilization. The use of metadynamics coupled with solute tempering results then particularly suitable to provide the thermodynamics of a short peptide, and its computational efficiency is promising to deal with larger proteins.

引用

页码：1647 / 1654

页数：8

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