Protein structure determination using metagenome sequence data

• DOI: 10.1126/science.aah4043
• Publication Date: 2017-01-19T19:00:59Z
• Authors: Sergey Ovchinnikov; Hahnbeom Park; Neha Varghese; Po-Ssu Huang; Georgios A. Pavlo...; David E. Kim; Hetunandan Kamisetty; Nikos C. Kyrpides; David Baker
• Keywords: Models, Molecular; 0301 basic medicine; 570; Protein Folding; Evolution; General Science & Technology; Protein Conformation; Bioinformatics and Computational Biology; Crystallography, X-Ray; Evolution, Molecular; Databases; 03 medical and health sciences; Models; Sequence Analysis, Protein; Amino Acid Sequence; Databases, Protein; Crystallography; Protein; Molecular; Computational Biology; Proteins; Biological Sciences; X-Ray; Metagenome; Biochemistry and Cell Biology; Sequence Analysis; Algorithms; Software

Filling in the protein fold picture

Fewer than a third of the 14,849 known protein families have at least one member with an experimentally determined structure. This leaves more than 5000 protein families with no structural information. Protein modeling using residue-residue contacts inferred from evolutionary data has been successful in modeling unknown structures, but it requires large numbers of aligned sequences. Ovchinnikov et al. augmented such sequence alignments with metagenome sequence data (see the Perspective by Söding). They determined the number of sequences required to allow modeling, developed criteria for model quality, and, where possible, improved modeling by matching predicted contacts to known structures. Their method predicted quality structural models for 614 protein families, of which about 140 represent newly discovered protein folds.

Science , this issue p. 294 ; see also p. 248