SSThread: Template‐free protein structure prediction by threading pairs of contacting secondary structures followed by assembly of overlapping pairs

Abstract

Acquiring the three-dimensional structure of a protein from its amino acid sequence alone, despite a great deal of work and significant progress on the subject, is still an unsolved problem. SSThread, a new template-free algorithm is described here that consists of making several predictions of contacting pairs of α-helices and β-strands derived from a database of experimental structures using a knowledge-based potential, secondary structure prediction, and contact map prediction followed by assembly of overlapping pair predictions to create an ensemble of core structure predictions whose loops are then predicted. In a set of seven CASP10 targets SSThread outperformed the two leading methods for two targets each. The targets were all β-strand containing structures and most of them have a high relative contact order which demonstrates the advantages of SSThread. The primary bottlenecks based on sets of 74 and 21 test cases are the pair prediction and loop prediction stages.