Monte Carlo Protein Folding: Simulations of Met-Enkephalin with Solvent-Accessible Area Parameterizations

TL;DR

This study evaluates solvent-accessible area parameterizations in Monte Carlo protein folding simulations of Met-Enkephalin, comparing different models and techniques to identify optimal conditions for efficient and accurate conformational sampling.

Contribution

It systematically compares nine ASP sets and other solvent models in Monte Carlo simulations, assessing their impact on sampling efficiency and energy minima detection.

Findings

Two ASP sets are unsuitable for simulations.

Unique minima found in vacuum and dielectric models, not in ASP models.

Autocorrelation times vary greatly with ASP parameters, affecting simulation speed.

Abstract

Treating realistically the ambient water is one of the main difficulties in applying Monte Carlo methods to protein folding. The solvent-accessible area method, a popular method for treating water implicitly, is investigated by means of Metropolis simulations of the brain peptide Met-Enkephalin. For the phenomenological energy function ECEPP/2 nine atomic solvation parameter (ASP) sets are studied that had been proposed by previous authors. The simulations are compared with each other, with simulations with a distance dependent electrostatic permittivity $\epsilon (r)$, and with vacuum simulations ($\epsilon =2$). Parallel tempering and a recently proposed biased Metropolis technique are employed and their performances are evaluated. The measured observables include energy and dihedral probability densities (pds), integrated autocorrelation times, and acceptance rates. Two of the ASP sets turn out to be unsuitable for these simulations. For all other sets, selected configurations are minimized in search of the global energy minima. Unique minima are found for the vacuum and the $\epsilon(r)$ system, but for none of the ASP models. Other observables show a remarkable dependence on the ASPs. In particular, autocorrelation times vary dramatically with the ASP parameters. Three ASP sets have much smaller autocorrelations at 300 K than the vacuum simulations, opening the possibility that simulations can be speeded up vastly by judiciously chosing details of the force