title: Exploring the free-energy landscape of a short peptide using an average force.
abstract: The reversible folding of deca-alanine is chosen as a test case for characterizing a method that uses an adaptive biasing force (ABF) to escape from the minima and overcome the barriers of the free-energy landscape. This approach relies on the continuous estimation of a biasing force that yields a Hamiltonian in which no average force is exerted along the ordering parameter xi. Optimizing the parameters that control how the ABF is applied, the method is shown to be extremely effective when a nonequivocal ordering parameter can be defined to explore the folding pathway of the peptide. Starting from a beta-turn motif and restraining xi to a region of the conformational space that extends from the alpha-helical state to an ensemble of extended structures, the ABF scheme is successful in folding the peptide chain into a compact alpha helix. Sampling of this conformation is, however, marginal when the range of xi values embraces arrangements of greater compactness, hence demonstrating the inherent limitations of free-energy methods when ambiguous ordering parameters are utilized.
authors.affiliation: Equipe de Dynamique des Assemblages Membranaires, UMR CNRS/UHP 7565, Institut Nancéien de Chimie Moléculaire, Université Henri Poincaré, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France. Christophe.Chipot@edam.uhp-nancy.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Chipot
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hénin
mesh_terms: D000409:Alanine / Q000737:chemistry*; D020816:Amino Acid Motifs; D002244:Carbon / Q000737:chemistry*; D002627:Chemistry, Physical / Q000379:methods*; D003198:Computer Simulation; D015233:Models, Statistical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D010455:Peptides; D002244:Carbon; D000409:Alanine