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

eLife

David Baker¹  Sergey Ovchinnikov²  David E Kim²  Hahnbeom Park²  Yuxing Liao³  Hetunandan Kamisetty⁴  Jimin Pei⁵  Nick V Grishin⁵  Lisa Kinch⁵ 

[1] Department of Biophysics, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States;Department of Biochemistry, University of Washington, Seattle, United States;Department of Biophysics, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States;Facebook Inc., Seattle, United States;Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States;

关键词: co-evolution;    structure prediction;    protein fold;    protein family;   

DOI  :  10.7554/eLife.09248

来源: DOAJ

【 摘 要 】

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 blindstructure 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.

【 授权许可】

Unknown