BackgroundProtein 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 lattice for structure mapping. For HP energy model, developing a compact hydrophobic-core (H-core) is essential for the progress of the search. The H-core helps find a stable structure with the lowest possible free energy.ResultsIn order to build H-cores, 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. We applied random walks to break premature H-cores and thus to avoid early convergence. We also used a novel relay-restart technique to handle stagnation.ConclusionsWe have tested our algorithms on a set of benchmark protein sequences. The experimental results show that our spiral search algorithm outperforms the state-of-the-art local search algorithms for simplified protein structure prediction. We also experimentally show the effectiveness of the relay-restart.

BackgroundGiven a protein's amino acid sequence, the protein structure prediction problem is to find a three dimensional structure that has the native energy level. For many decades, it has been one of the most challenging problems in computational biology. A simplified version of the problem is to find an on-lattice self-avoiding walk that minimizes the interaction energy among the amino acids. Local search methods have been preferably used in solving the protein structure prediction problem for their efficiency in finding very good solutions quickly. However, they suffer mainly from two problems: re-visitation and stagnancy.ResultsIn this paper, we present an efficient local search algorithm that deals with these two problems. During search, we select the best candidate at each iteration, but store the unexplored second best candidates in a set of elite conformations, and explore them whenever the search faces stagnation. Moreover, we propose a new non-isomorphic encoding for the protein conformations to store the conformations and to check similarity when applied with a memory based search. This new encoding helps eliminate conformations that are equivalent under rotation and translation, and thus results in better prevention of re-visitation.ConclusionOn standard benchmark proteins, our algorithm significantly outperforms the state-of-the art approaches for Hydrophobic-Polar energy models and Face Centered Cubic Lattice.

The travelling thief problem (TTP) is a combination of two interdependent NP-hard components: travelling salesman problem (TSP) and knapsack problem (KP). Existing approaches for TTP typically solve the TSP and KP components in an interleaved fashion, where the solution to one component is held fixed while the other component is changed. This indicates poor coordination between solving the two components and may lead to poor quality TTP solutions. For solving the TSP component, the 2-OPT segment reversing heuristic is often used for modifying the tour. We propose an extended and modified form of the reversing heuristic in order to concurrently consider both the TSP and KP components. Items deemed as less profitable and picked in cities earlier in the reversed segment are replaced by items that tend to be equally or more profitable and not picked in the later cities. Comparative evaluations on a broad range of benchmark TTP instances indicate that the proposed approach outperforms existing state-of-the-art TTP solvers.