Parametrization of a new coarse grained forcefield for multiscale simulation of protein folding

AVILA CL; DRESCHEL NJD; VILLÀ-FREIXA J; CHEHIN, RN

Cordoba

Workshop; 1er Workshop Argentino de Biofísicoquímica de Proteinas; 2011

Introduction: Despite important progress during the last few years, with all-atom simulations achieving high accuracy models (resolution < 1.0 A) for small proteins, ab-initio protein folding simulation is still a challenge to the scientific community. Due to the high computational demand of these methods, they still cannot be used for studying folding of medium to large proteins. This has led to a quest for simplified, coarse-grained (CG), protein models with physically accurate conformational energetics rivaling all-atom models. Additionaly, multiscale techniques have recently emerged as a promising tool to explore molecular systems in an integral way and several methods have been proposed to bridge the different level of detail underlying each model. A basic requirement for a coarse-grained model to be used in these schemes is that it must be physically realistic so that the structures being sampled represent relevant conformations of the protein. Objectives: In this work, we develop and parametrize a new coarse-grained protein model based on the Amber 96 forcefield. Results: The functional form of the new CG forcefield is introduced, along with the parameters set. Its ability to sample the conformational space for some experimentally well characterized fast- folding proteins is evaluated. Conclusion: The results presented herein open a door for future use of this force-field as a reference potential in multiscale approaches of protein folding.