A new combination of replica exchange Monte Carlo and histogram analysis for protein folding and thermodynamics

A novel combination of replica exchange Monte Carlo sampling techniques wit h a histogram analysis approach is developed and applied to study the therm odynamics of the folding transition in a face-centered cubic lattice chain protein model. Sequences of hydrophobic (H) and polar (P) topology residues were designed to fold into various beta -barrel type proteins. The interac tion scheme includes the short-range propensity to form extended conformati ons, residue-dependent long-range contact potentials, and orientation-depen dent hydrogen bonds. Weakly cooperative folding transitions could be observ ed for properly designed HP. (Hydrophobic and polar residue sequences with cooperative long-range interaction methods were proposed and tested.) Based on the study of these systems, the computational cost of such an approach is many times less than the cost of other Monte Carlo procedures. This open s up the possibility for efficient studies of the folding thermodynamics of more detailed protein models. (C) 2001 American Institute of Physics.