Contact-based simulated annealing protein sequence alignment method

Protein sequence alignments reveal the evolutionary information between homologous sequences. Traditional sequence alignment methods only use sequence information and the structure information from template Is ignored. Recently, Kleinjung et al. developed a contact-based sequence alignment method that used the structural information from side-chain contacts. Alignment scores are provided by the CAO (Contact Accepted mutatiOn) substitution matrices. Kleinjung et al. devised an approximate dynamic programming algorithm for protein sequence alignment, on the assumption that the distance between the contacting residues during evolution has been conserved. However, such assumption is not suitable for insertion/deletion events during evolution. In this paper, the contact-based simulated annealing alignment method has been proposed, which can find the optimal alignment solution between two protein sequences without any restriction. The alignment score is calculated by the sequence-based scores and the weighted contact-based scores. A new parameter, the contact-penalty r, has been introduced. When the contacting residue in the template aligns with gap in the query sequence, the total alignment score is decreased by a contact-penalty. All the parameters including relative weight w of CAO scores versus Blosum62 scores, matrix constant c for CAO scores, gap-open penalty p, gap-extension penalty q and contact-penalty r are re-optimized by genetic algorithm. Testing on the Homstrad database shows that the accuracy of this method is 85.4%, which is higher than that of Kleinjung's method by about 3.6 percent. Such method can be useful in many biological problems such as protein remote homology detection, comparative modeling and fold recognition.