Exploring the Protein G Helix Free Energy Surface by Solute Tempering Metadynamics
Abstract
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.
Keywords
Cite
@article{arxiv.0707.1230,
title = {Exploring the Protein G Helix Free Energy Surface by Solute Tempering Metadynamics},
author = {C. Camilloni and D. Provasi and G. Tiana and R. A. Broglia},
journal= {arXiv preprint arXiv:0707.1230},
year = {2007}
}