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

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.

[1]  Vincent B. Chen,et al.  Correspondence e-mail: , 2000 .

[2]  Alexander D. MacKerell,et al.  Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles. , 2012, Journal of chemical theory and computation.

[3]  Alexander D. MacKerell,et al.  All-atom empirical potential for molecular modeling and dynamics studies of proteins. , 1998, The journal of physical chemistry. B.

[4]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[5]  Stephen L. Mayo,et al.  GRID: A high‐resolution protein structure refinement algorithm , 2013, J. Comput. Chem..

[6]  Yang Zhang,et al.  A Novel Side-Chain Orientation Dependent Potential Derived from Random-Walk Reference State for Protein Fold Selection and Structure Prediction , 2010, PloS one.

[7]  Jianhan Chen,et al.  Can molecular dynamics simulations provide high‐resolution refinement of protein structure? , 2007, Proteins.

[8]  Nicholas P. Schafer,et al.  AWSEM-MD: protein structure prediction using coarse-grained physical potentials and bioinformatically based local structure biasing. , 2012, The journal of physical chemistry. B.

[9]  Mark A. Olson,et al.  Comparison between self‐guided Langevin dynamics and molecular dynamics simulations for structure refinement of protein loop conformations , 2011, J. Comput. Chem..

[10]  Michael Feig,et al.  MMTSB Tool Set: enhanced sampling and multiscale modeling methods for applications in structural biology. , 2004, Journal of molecular graphics & modelling.

[11]  Debswapna Bhattacharya,et al.  3Drefine: Consistent protein structure refinement by optimizing hydrogen bonding network and atomic‐level energy minimization , 2013, Proteins.

[12]  Hongyi Zhou,et al.  Distance‐scaled, finite ideal‐gas reference state improves structure‐derived potentials of mean force for structure selection and stability prediction , 2002, Protein science : a publication of the Protein Society.

[13]  Yang Zhang.  Protein structure prediction: when is it useful? , 2009, Current opinion in structural biology.

[14]  Matthew P Jacobson,et al.  Assessment of protein structure refinement in CASP9 , 2011, Proteins.

[15]  R. Dror,et al.  How Fast-Folding Proteins Fold , 2011, Science.

[16]  Krzysztof Fidelis,et al.  CASP10 results compared to those of previous CASP experiments , 2014, Proteins.

[17]  Jens Meiler,et al.  Iterative Molecular Dynamics—Rosetta Protein Structure Refinement Protocol to Improve Model Quality , 2013, Journal of chemical theory and computation.

[18]  Keehyoung Joo,et al.  Refinement of protein termini in template‐based modeling using conformational space annealing , 2011, Proteins.

[19]  Vahid Mirjalili,et al.  Protein Structure Refinement through Structure Selection and Averaging from Molecular Dynamics Ensembles. , 2013, Journal of chemical theory and computation.

[20]  Timothy Nugent,et al.  Accurate de novo structure prediction of large transmembrane protein domains using fragment-assembly and correlated mutation analysis , 2012, Proceedings of the National Academy of Sciences.

[21]  Hui Lu,et al.  Application of statistical potentials to protein structure refinement from low resolution ab initio models , 2003, Biopolymers.

[22]  Chaok Seok,et al.  GalaxyRefine: protein structure refinement driven by side-chain repacking , 2013, Nucleic Acids Res..

[23]  Michael S. Lee,et al.  Evaluation of Unrestrained Replica-Exchange Simulations Using Dynamic Walkers in Temperature Space for Protein Structure Refinement , 2014, PloS one.

[24]  David Baker,et al.  The origin of consistent protein structure refinement from structural averaging. , 2015, Structure.

[25]  Michael Levitt,et al.  Near-native structure refinement using in vacuo energy minimization , 2007, Proceedings of the National Academy of Sciences.

[26]  Vahid Mirjalili,et al.  Physics‐based protein structure refinement through multiple molecular dynamics trajectories and structure averaging , 2014, Proteins.

[27]  Laxmikant V. Kalé,et al.  Scalable molecular dynamics with NAMD , 2005, J. Comput. Chem..

[28]  Chaok Seok,et al.  Refinement of unreliable local regions in template‐based protein models , 2012, Proteins.

[29]  James M Aramini,et al.  Assessment of template‐based protein structure predictions in CASP10 , 2014, Proteins.

[30]  Abhinandan Jain,et al.  Protein Structure Refinement of CASP Target Proteins Using GNEIMO Torsional Dynamics Method , 2014, J. Chem. Inf. Model..

[31]  David T Jones,et al.  Evaluation of predictions in the CASP10 model refinement category , 2013, Proteins.

[32]  Yun-Dong Wu,et al.  Significant Refinement of Protein Structure Models Using a Residue-Specific Force Field. , 2015, Journal of chemical theory and computation.

[33]  Michael Levitt,et al.  KoBaMIN: a knowledge-based minimization web server for protein structure refinement , 2012, Nucleic Acids Res..

[34]  Yang Zhang,et al.  Automated protein structure modeling in CASP9 by I‐TASSER pipeline combined with QUARK‐based ab initio folding and FG‐MD‐based structure refinement , 2011, Proteins.

[35]  Michael Feig,et al.  Sampling of near‐native protein conformations during protein structure refinement using a coarse‐grained model, normal modes, and molecular dynamics simulations , 2007, Proteins.

[36]  M Feig,et al.  Accurate reconstruction of all‐atom protein representations from side‐chain‐based low‐resolution models , 2000, Proteins.