Folding helical proteins in explicit solvent using dihedral-biased tempering

TLDR: Using a single-trajectory-based tempering method with a high-temperature dihedral bias, four helical proteins were folded and some of the mutants in explicit solvent within several microseconds and the native conformation usually occupied the most populated cluster.

Abstract: Using a single-trajectory-based tempering method with a high-temperature dihedral bias, we repeatedly folded four helical proteins [α3D (PDB ID: 2A3D, 73 residues), α3W (1LQ7, 67 residues), Fap1-NRα (2KUB, 81 residues) and S-836 (2JUA, 102 residues)] and some of the mutants in explicit solvent within several microseconds. The lowest root-mean-square deviations of backbone atoms from the experimentally determined structures were 1.9, 1.4, 1.0, and 2.1 A, respectively. Cluster analyses of folding trajectories showed the native conformation usually occupied the most populated cluster. The simulation protocol can be applied to large-scale simulations of other helical proteins on commonly accessible computing platforms.