Free-energy landscape for beta hairpin folding from combined parallel tempering and metadynamics.
We develop a new free-energy method, based on the combination of parallel tempering and metadynamics, and apply this method to the calculation of the free-energy landscape of the folding beta hairpin in explicit water. We show that the combined method greatly improves the performance of both parallel tempering and metadynamics. In particular, we are able to sample the high free-energy regions, which are not accessible with conventional parallel tempering. We use our results to calculate the difference in entropy and enthalpy between the folded and the unfolded state and to characterize the most populated configurations in the relevant free-energy basins.
Bussi
Giovanni
G
Computational Science, Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule Zürich, c/o USI Campus, Via Buffi 13, CH-6900 Lugano, Switzerland. gbussi@ethz.ch
Gervasio
Francesco Luigi
FL
Laio
Alessandro
A
Parrinello
Michele
M
D000465:Algorithms; D003198:Computer Simulation; D006860:Hydrogen Bonding; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D010455:Peptides; D014867:Water