The other 90% of the protein: Assessment beyond the Cαs for CASP8 template-based and high-accuracy models

By Daniel A. Keedy, Christopher J. Williams, J. Headd, W. B. Arendall, Vincent B. Chen, Gary J. Kapral, R. Gillespie, Jeremy N. Block, Adam T. Zemla, David C Richardson and 1 more. 2009

84 citations recorded by the source corpus.

For template‐based modeling in the CASP8 Critical Assessment of Techniques for Protein Structure Prediction, this work develops and applies six new full‐model metrics. They are designed to complement and add value to the traditional template‐based assessment by the global distance test (GDT) and related scores (based on multiple superpositions of Cα atoms between target structure and predictions labeled “Model 1”). The new metrics evaluate each predictor group on each target, using all atoms of their best model with above‐average GDT. Two metrics evaluate how “protein‐like” the predicted model is: the MolProbity score used for validating experimental structures, and a mainchain reality score using all‐atom steric clashes, bond length and angle outliers, and backbone dihedrals. Four other new metrics evaluate match of model to target for mainchain and sidechain hydrogen bonds, sidechain end positioning, and sidechain rotamers. Group‐average Z‐score across the six full‐model measures is averaged with group‐average GDT Z‐score to produce the overall ranking for full‐model, high‐accuracy performance. Separate assessments are reported for specific aspects of predictor‐group performance, such as robustness of approximately correct template or fold identification, and self‐scoring ability at identifying the best of their models. Fold identification is distinct from but correlated with group‐average GDT Z‐score if target difficulty is taken into account, whereas self‐scoring is done best by servers and is uncorrelated with GDT performance. Outstanding individual models on specific targets are identified and discussed. Predictor groups excelled at different aspects, highlighting the diversity of current methodologies. However, good full‐model scores correlate robustly with high Cα accuracy. Proteins 2009. © 2009 Wiley‐Liss, Inc.

Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology

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Citations in the corpus

lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests (2013, methodology): “…the local modeling quality were introduced (main chain reality score, hydrogen bond correctness, rotamer correctness and side-chain positioning) (Keedy et al., 2009), as well as an evaluation of the stereochemical realism and plausibility of models using the MolProbity score (Chen et al., 2010).”
High resolution comparative modeling with RosettaCM (2013, methodology): “, (C,D) accuracy of sidechain placement, as measured by the GDC-SC metric(Keedy et al., 2009), (E,F) stereochemical quality, as assesed by the Molprobity score(Davis et al., 2007”
Alternate states of proteins revealed by detailed energy landscape mapping (2010, neutral): “This score was recently employed for homology model assessment and is described in more detail elsewhere.(33)”
Assessment of template based protein structure predictions in CASP9 (2011, background): “19,20 In the template based modeling category, all models can be expected to be physically realistic and plausible.”
GalaxyRefine: protein structure refinement driven by side-chain repacking (2013, methodology): “The test results in terms of improvement of model 1 (and the best refined model out of model 1–5) over initial input models for backbone structure accuracy measured by GDT-HA (13), side-chain structure accuracy measured by GDC-SC (14) and physical correctness measured by MolProbity score (15) are su”
CAD‐score: A new contact area difference‐based function for evaluation of protein structural models (2013, background): “13,14 To make the score mindful of steric clashes, the inclusion of repulsion term into GDT-TS was proposed.”
Atomic-level protein structure refinement using fragment guided molecular dynamics conformation sampling (2011, methodology): “…structures often contain significant local distortions, including steric clashes, unphysical phi/psi angles, and irregular hydrogenbonding (H-bonding) networks, which render the structure models less useful for high-resolution functional analysis (Arakaki et al., 2004; Keedy et al., 2009).”
Assessment of protein structure refinement in CASP9 (2011, methodology): “We use a combination of these terms, defined as the MPscore [22, 23].”
Assessment of Refinement of Template-Based Models in CASP11 (2016, background): “23,24 A lower score indicates that the residues of the model have better stereochemistry than models with higher scores.”