title: CASP11--An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline.
abstract: In silico prediction of a protein's tertiary structure remains an unsolved problem. The community-wide Critical Assessment of Protein Structure Prediction (CASP) experiment provides a double-blind study to evaluate improvements in protein structure prediction algorithms. We developed a protein structure prediction pipeline employing a three-stage approach, consisting of low-resolution topology search, high-resolution refinement, and molecular dynamics simulation to predict the tertiary structure of proteins from the primary structure alone or including distance restraints either from predicted residue-residue contacts, nuclear magnetic resonance (NMR) nuclear overhauser effect (NOE) experiments, or mass spectroscopy (MS) cross-linking (XL) data. The protein structure prediction pipeline was evaluated in the CASP11 experiment on twenty regular protein targets as well as thirty-three 'assisted' protein targets, which also had distance restraints available. Although the low-resolution topology search module was able to sample models with a global distance test total score (GDT_TS) value greater than 30% for twelve out of twenty proteins, frequently it was not possible to select the most accurate models for refinement, resulting in a general decay of model quality over the course of the prediction pipeline. In this study, we provide a detailed overall analysis, study one target protein in more detail as it travels through the protein structure prediction pipeline, and evaluate the impact of limited experimental data.
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, United States of America.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Axel W
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, United States of America.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Sten
authors.initials: S
authors.lastname: Heinze
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Putnam
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, United States of America.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Bian
authors.initials: B
authors.lastname: Li
authors.affiliation: Chemical and Physical Biology Graduate Program, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Pino
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, United States of America.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.|Department of Cancer Biology and Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lopez
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, United States of America.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37232, United States of America.
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017434:Protein Structure, Tertiary