CASP11--An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline.

Fischer AW, Heinze S, Putnam DK, Li B, Pino JC, Xia Y, Lopez CF, Meiler J
PLoS One. 2016 11 (4): e0152517

PMID: 27046050 · PMCID: PMC4821492 · DOI:10.1371/journal.pone.0152517

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.

MeSH Terms (5)

Magnetic Resonance Spectroscopy Mass Spectrometry Molecular Dynamics Simulation Protein Folding Protein Structure, Tertiary

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