A new procedure for constructing peptides into a given Calpha chain.

Abstract

BACKGROUND: In ab initio protein folding studies, it is often advantageous to build the Calpha chain first and then to construct the full structure by filling in the peptide groups and the sidechains. Many algorithms have been reported for constructing peptide groups on the Calpha chain, but most are unsuitable for use in such studies; some are too slow for screening a large number of trial Calpha chains and others use only the local geometry and ignore the effects of specific non-neighbor interactions, which can be crucial for proper folding. We needed a fast procedure for constructing the peptide groups that does not ignore the effects of long-range, specific interactions. RESULTS: We first found rich correlations between the peptide orientation angle and both the local Calpha-chain geometry and the type of the flanking amino acid residues. These correlations can be used to greatly limit the range of possible peptide orientation angles. We devised a simple peptide construction procedure in which all orientations within this reduced range are systematically examined and the orientation is selected that minimizes a suitable energy function that includes long-range, specific interactions. When tested on known structures, the method is found to be among the fastest of known methods and attains an accuracy comparable with or better than most methods. CONCLUSIONS: The new method is fast and takes into account both the local and non-local specific interactions. It therefore appears to be suitable for use in ab initio protein folding studies, wherein a large number of Calpha chains are screened.