title: A bias-exchange approach to protein folding.
abstract: By suitably extending a recent approach [Bussi, G.; et al. J. Am. Chem. Soc. 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at the same temperature are performed, biasing each replica with a time-dependent potential constructed in a different set of collective variables. Exchanges between the bias potentials in the different variables are periodically allowed according to a replica exchange scheme. Due to the efficaciously multidimensional nature of the bias the method allows exploring complex free energy landscapes with high efficiency. The usefulness of the method is demonstrated by performing an atomistic simulation in explicit solvent of the folding of a Triptophane cage miniprotein. It is shown that the folding free energy landscape can be fully characterized starting from an extended conformation with use of only 40 ns of simulation on 8 replicas.
authors.affiliation: International School for Advanced Studies (SISSA/ISAS), Via Beirut 2-4, Trieste, Italy, and Nanochemistry Research Institute, Curtin University of Technology, GPO Box U1987, Perth 6845, Western Australia. piana@power.curtin.edu.au
authors.forename: Stefano
authors.initials: S
authors.lastname: Piana
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011336:Probability; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins