Protein structure prediction using Rosetta in CASP12

• Published in: Proteins, structure, function, and bioinformatics Vol. 86; no. S1; pp. 113 - 121
• Main Authors: Ovchinnikov, Sergey, Park, Hahnbeom, Kim, David E., DiMaio, Frank, Baker, David
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-03-2018
• Subjects: ab initio prediction; Algorithms; Computational Biology - methods; Computer simulation; co‐evolution; Crystal structure; Crystallography, X-Ray; Homology; Humans; Mathematical models; Modelling; Models, Molecular; Predictions; Protein Conformation; Protein families; Protein Folding; Protein structure; protein structure prediction; Proteins; Proteins - chemistry; refinement; Rosetta; Sequence Analysis, Protein; ab initio prediction; refinement; protein structure prediction; Rosetta; co-evolution
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.25390

We describe several notable aspects of our structure predictions using Rosetta in CASP12 in the free modeling (FM) and refinement (TR) categories. First, we had previously generated (and published) models for most large protein families lacking experimentally determined structures using Rosetta guided by co‐evolution based contact predictions, and for several targets these models proved better starting points for comparative modeling than any known crystal structure—our model database thus starts to fulfill one of the goals of the original protein structure initiative. Second, while our “human” group simply submitted ROBETTA models for most targets, for six targets expert intervention improved predictions considerably; the largest improvement was for T0886 where we correctly parsed two discontinuous domains guided by predicted contact maps to accurately identify a structural homolog of the same fold. Third, Rosetta all atom refinement followed by MD simulations led to consistent but small improvements when starting models were close to the native structure, and larger but less consistent improvements when starting models were further away.