An extension of dead end elimination for protein side-chain conformation using merge-decoupling

Abstract

A two-phase strategy is widely adopted to solve the side-chain conformation prediction (SCCP) problem. Phase one is a fast reduction phase removing large numbers of rotamers not existing in the GMEC. Phase two (optimization phase) uses heuristics or exhaustive search to find a good/optimal solution. Presently, DEE (Dead End Elimination) is the only deterministic reduction method for phase one. However, to achieve convergence in phase two using DEE, the strategy of forming super-residues is used. This quickly leads to a combinatorial explosion, and becomes inefficient In this paper, an improvement of the DEE process by forming super-residues efficiently is proposed for phase one. The method basically merges residues into pairs based on some merging criteria. Simple Goldstein is then applied until no more elimination is possible. A decoupling process then reforms the original residues sans removed rotamers and rotamer pairs. The process of merging and elimination is repeated until no more elimination is possible. Initial experiments have shown the method, called Merge-Decoupling DEE, can fix up to 25% of the unfixed residues coming out of Simple Goldstein DEE.