Combine Cryo-EM Density Map and Residue Contact for Protein Structure Prediction - A Case Study.

Abstract

Cryo-electron microscopy is a major structure determination technique for large molecular machines and membrane-associated complexes. Although atomic structures have been determined directly from cryo-EM density maps with high resolutions, current structure determination methods for medium resolution (5 to 10 Å) cryo-EM maps are limited by the availability of structure templates. Secondary structure traces are lines detected from a cryo-EM density map for α-helices and β-strands of a protein. When combined with secondary structure sequence segments predicted from a protein sequence, it is possible to generate a set of likely topologies of α-traces and β-sheet traces. A topology describes the overall folding relationship among secondary structures; it is a critical piece of information for deriving the corresponding atomic structure. We propose a method for protein structure prediction that combines three sources of information: the secondary structure traces detected from the cryo-EM density map, predicted secondary structure sequence segments, and amino acid contact pairs predicted using MULTICOM. A case study shows that using amino acid contact prediction from MULTICOM improves the ranking of the true topology. Our observations convey that using a small set of highly voted secondary structure contact pairs enhances the ranking in all experiments conducted for this case.