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. 2016 Sep;84 Suppl 1(Suppl 1):282-92.
doi: 10.1002/prot.24871. Epub 2015 Aug 17.

Protein structure refinement via molecular-dynamics simulations: What works and what does not?

Michael Feig  1   2 , Vahid Mirjalili  3   4
Affiliations

Protein structure refinement via molecular-dynamics simulations: What works and what does not?

Michael Feig et al. Proteins. 2016 Sep.

Abstract

Protein structure refinement during CASP11 by the Feig group was described. Molecular dynamics simulations were used in combination with an improved selection and averaging protocol. On average, modest refinement was achieved with some targets improved significantly. Analysis of the CASP submission from our group focused on refinement success versus amount of sampling, refinement of different secondary structure elements and whether refinement varied as a function of which group provided initial models. The refinement of local stereochemical features was examined via the MolProbity score and an updated protocol was developed that can generate high-quality structures with very low MolProbity scores for most starting structures with modest computational effort. Proteins 2016; 84(Suppl 1):282-292. © 2015 Wiley Periodicals, Inc.

Keywords: CASP; Molprobity; protein; scoring; structure prediction.

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Figures

Figure 1
Figure 1
Refinement protocol of FEIG group during CASP11.
Figure 2
Figure 2
GDT-HA scores of model 1 submissions from the FEIG group (red) and best snapshots generated during sampling for each target (grey) vs. GDT-HA scores of initial models provided by CASP.
Figure 3
Figure 3
Cα RMSD values of model 1 submissions from the FEIG group (red) and best snapshots generated during sampling for each target (grey) vs. Cα RMSD values of initial models provided by CASP.
Figure 4
Figure 4
Successful and unsuccessful refinement in target TR759. The experimental reference is shown in red, the initial model provided by CASP in green, and the refined model submitted by us in blue. Residues 75–94 (successful refinement) and residues 53–60 (unsuccessful refinement) are highlighted with saturated colors.
Figure 5
Figure 5
Average improvement of GDT-HA score for 35 CASP11 refinement targets as a function of total simulation time using snapshots from 1–40 trajectories over 2 ns (blue), 10 ns (green), 20 ns (brown), or 30 ns (red).
Figure 6
Figure 6
Protocol for optimization of MolProbity applied in CASP11 post-analysis.
See this image and copyright information in PMC

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