Large-scale determination of previously unsolved protein structures using evolutionary information

• Published in: eLife Vol. 4; p. e09248
• Main Authors: Ovchinnikov, Sergey, Kinch, Lisa, Park, Hahnbeom, Liao, Yuxing, Pei, Jimin, Kim, David E, Kamisetty, Hetunandan, Grishin, Nick V, Baker, David
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications, Ltd 03-09-2015; eLife Sciences Publications Ltd
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Biophysics and Structural Biology; co-evolution; Computational Biology - methods; Evolution, Molecular; Genomics and Evolutionary Biology; Models, Molecular; Protein Conformation; protein family; protein fold; structure prediction; B. subtilis; S. solfataricus; evolutionary biology; structure prediction; H. salinarum; protein family; genomics; protein fold; structural biology; biophysics; E. coli; co-evolution
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.09248

The prediction of the structures of proteins without detectable sequence similarity to any protein of known structure remains an outstanding scientific challenge. Here we report significant progress in this area. We first describe de novo blind structure predictions of unprecendented accuracy we made for two proteins in large families in the recent CASP11 blind test of protein structure prediction methods by incorporating residue-residue co-evolution information in the Rosetta structure prediction program. We then describe the use of this method to generate structure models for 58 of the 121 large protein families in prokaryotes for which three-dimensional structures are not available. These models, which are posted online for public access, provide structural information for the over 400,000 proteins belonging to the 58 families and suggest hypotheses about mechanism for the subset for which the function is known, and hypotheses about function for the remainder.