Premium
Exploring the protein G helix free‐energy surface by solute tempering metadynamics
Author(s) -
Camilloni Carlo,
Provasi Davide,
Tiana Guido,
Broglia Ricardo A.
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21852
Subject(s) - metadynamics , energy landscape , metastability , parallel tempering , molecular dynamics , chemistry , tempering , helix (gastropod) , crystallography , globular protein , chemical physics , computational chemistry , statistical physics , thermodynamics , materials science , physics , monte carlo method , mathematics , markov chain monte carlo , biochemistry , organic chemistry , ecology , statistics , snail , monte carlo molecular modeling , composite material , biology
The free‐energy landscape of the α‐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 β‐structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a π‐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. Proteins 2008. © 2007 Wiley‐Liss, Inc.