A replica exchange Monte Carlo algorithm for the optimization of secondary structure packing in proteins

Abstract

We approach the problem of packing secondary structure fragments into low energy conformations with a local search optimization algorithm. Protein conformations are represented in a simplified off-lattice model. In that model we propose a move set that transforms a protein conformation into another in order to enable the use of local search algorithms for protein folding simulations and conformational search. The energy minimization problem behind protein folding is adapted to our model. Special care has been taken so that amino acids in a conformation do not overlap. The constraint of producing an overlap-free conformation can be seen as a objective that conflicts with the energy minimization. Thus, we approach protein folding as a two-objective problem. We employ a replica exchange Monte Carlo algorithm in combination to the proposed move set. The algorithm deals with the energy minimization problem while maintaining overlap-free conformations. Initial conformations incorporate experimentally determined secondary structure, which is preserved throughout the execution of local search. Our method produced conformations with a minimum RMSD of alpha-carbon atoms in the range of 4.71Å to 6.82Å for all benchmarks apart from one for which the value was 9.68Å. © 2010 Springer-Verlag Berlin Heidelberg.