Prediction of protein secondary structure with a reliability score estimated by local sequence clustering.

Abstract

Most algorithms for protein secondary structure prediction are based on machine learning techniques, e.g. neural networks. Good architectures and learning methods have improved the performance continuously. The introduction of profile methods, e.g. PSI-BLAST, has been a major breakthrough in increasing the prediction accuracy to close to 80%. In this paper, a brute-force algorithm is proposed and the reliability of each prediction is estimated by a z-score based on local sequence clustering. This algorithm is intended to perform well for those secondary structures in a protein whose formation is mainly dominated by the neighboring sequences and short-range interactions. A reliability z-score has been defined to estimate the goodness of a putative cluster found for a query sequence in a database. The database for prediction was constructed by experimentally determined, non-redundant protein structures with <25% sequence homology, a list maintained by PDBSELECT. Our test results have shown that this new algorithm, belonging to what is known as nearest neighbor methods, performed very well within the expectation of previous methods and that the reliability z-score as defined was correlated with the reliability of prediction. This led to the possibility of making very accurate predictions for a few selected residues in a protein with an accuracy measure of Q3 > 80%. The further development of this algorithm, and a nucleation mechanism for protein folding are suggested.