3D protein structure prediction with genetic tabu search algorithm

Abstract

Background: Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task.

Results: In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods.

Conclusions: The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill-climbing capability in the conventional genetic algorithm by using the flexible memory functions of TS. Compared with some previous algorithms, GATS algorithm has better performance in global optimization and can predict 3D protein structure more effectively.

Figure 1

TSM process TSM is a search process. With this strategy, the potential energy functional in equation (1) is used as the evaluation function to compute offspring’s energy values, and then these offspring and their energies are combined with the tabu list to determine the output offspring.

Figure 2

Genetic tabu search algorithm The hybrid algorithm combines genetic algorithm and tabu search algorithm and can deal with multi-extremum and multi-parameter problems.

Figure 3

The lowest energy conformations for the four Fibonacci sequences obtained by GATS algorithm Solid dots indicate hydrophobic monomers A, and open dots indicate hydrophilic monomers B.

Figure 4

The lowest energy conformations for the three real protein sequences obtained by GATS algorithm Solid dots indicate hydrophobic monomers I, V, L, P, C, M, A, G, and open dots indicate hydrophilic monomers D, E, F, H, K, N, Q, R, S, T, W, Y.