CReF

Abstract

In silico prediction of protein tertiary structure is one of the most important and unsolved problems in current structural bioinformatics. In this article, we describe CReF, a central-residue-fragment-based method to predict approximate 3-D polypeptides structures. With CReF we expect to obtain approximate 3-D structures which can then be used as starting conformations in refinement procedures employing state-of-the-art molecular mechanics methods such as molecular dynamics simulations. CReF does not make use of entire fragments, but only the phi, psi torsion angle information of the central residue in the template fragments obtained from PDB. After applying clustering techniques to these data, and guided by a consensus secondary structure prediction of the target sequence, we build approximate conformations for the target sequence. The method is very fast. We illustrate its efficacy in three case studies of polypeptides whose sizes vary from 34 to 70 amino acids. As indicated by the RMSD values, our initial results show that the predicted conformations adopt a fold similar to the experimental structures. Starting from these approximate conformations, the search space is expected to be greatly reduced and the refinement steps can consequently demand a much reduced computational effort to achieve a more accurate polypeptide 3-D structure.