Potential energy surfaces and conformational transitions in biomolecules: a successive confinement approach applied to a solvated tetrapeptide.

A simple approach for the efficient exploration of the potential energy surface of a many-body system is presented. The method uses Langevin dynamics trajectories that are successively confined in the various basins of the potential energy surface. The approach is illustrated by determining the potential energy surface, and the thermodynamic and kinetic properties of a solvated model for the alanine tetrapeptide, the shortest peptide that can form an alpha-helical turn. All possible cis isomers are sampled, even though the barriers separating them are as high as 25 kcal/mole. Comparisons with conventional Langevin dynamics confirm the greater efficacy of the approach.