Spiral Search: A Hydrophobic-Core Directed Local Search for Simplified PSP on 3D FCC Lattice

Abstract

Background: Protein structure prediction is an important but unsolved problem in biological science. Predicted structures vary much with energy functions and structure-mapping spaces. In our simplified ab initio protein structure prediction methods, we use hydrophobic-polar (HP) energy model for structure evaluation, and 3-dimensional face-centred-cubic (FCC) lattice for structure mapping. For HP energy model, developing a compact hydrophobic-core (HC) is essential for the progress of the search. The hydrophobic-core (H-core) helps find a stable structure with the lowest possible free energy. Results: In order to build H-core, we present a new Spiral Search algorithm based on tabu-guided local search. Our algorithm uses a novel H-core directed guidance heuristic that squeezes the structure around a dynamic hydrophobic-core-centre (HCC). We applied random-walk for breaking premature H-cores to avoid early convergence. We used a novel relay-restart (RR) technique to handle stagnation. Conclusions: We tested our algorithms on a set of benchmark proteins. The experimental results show that our spiral search performs better in comparison to state-of-the art local search algorithms for simplified protein structure prediction. We also experimentally show the effectiveness of the relay-restart.