Efficient dynamics in the space of contact maps

Abstract

Two problems are of major importance in protein fold prediction: how to generate plausible conformations, and how to choose an energy function to identify the native state. Contact maps are a simple representation of protein structure and offer a promising framework to address these two issues. In this work we develop Monte Carlo dynamics in contact map space. The procedure is divided into four steps: non-local dynamics, in which large-scale "cluster" moves are performed (clusters are in approximate correspondence with secondary structure elements); local dynamics, in which secondary structure location is optimized; reconstruction, in which the physicality of the contact map is restored; and refinement, which consists of a further Monte Carlo energy minimization in real space. We demonstrate that such a dynamical procedure is effective in producing uncorrelated low-energy states. The procedure introduced in this paper very effectively generates a representative ensemble of conformations. We are able to show that existing sets of pairwise contact energy parameters are not suitable to single out the native state within this ensemble. The remaining outstanding issue in protein folding is to find an energy function that can discriminate the native state from decoys.