WeFold: A coopetition for protein structure prediction

The protein structure prediction problem continues to elude scientists. Despite the introduction of many methods, only modest gains were made over the last decade for certain classes of prediction targets. To address this challenge, a social‐media based worldwide collaborative effort, named WeFold, was undertaken by 13 labs. During the collaboration, the laboratories were simultaneously competing with each other. Here, we present the first attempt at “coopetition” in scientific research applied to the protein structure prediction and refinement problems. The coopetition was possible by allowing the participating labs to contribute different components of their protein structure prediction pipelines and create new hybrid pipelines that they tested during CASP10. This manuscript describes both successes and areas needing improvement as identified throughout the first WeFold experiment and discusses the efforts that are underway to advance this initiative. A footprint of all contributions and structures are publicly accessible at http://www.wefold.org. Proteins 2014; 82:1850–1868. © 2014 Wiley Periodicals, Inc.

[1]  R. Swendsen,et al.  THE weighted histogram analysis method for free‐energy calculations on biomolecules. I. The method , 1992 .

[2]  K Fidelis,et al.  A large‐scale experiment to assess protein structure prediction methods , 1995, Proteins.

[3]  A. Liwo,et al.  A united‐residue force field for off‐lattice protein‐structure simulations. I. Functional forms and parameters of long‐range side‐chain interaction potentials from protein crystal data , 1997 .

[4]  S. Bryant,et al.  Critical assessment of methods of protein structure prediction (CASP): Round II , 1997, Proteins.

[5]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997, J. Comput. Chem..

[6]  Adam Liwo,et al.  A united-residue force field for off-lattice protein-structure simulations. I. Functional forms and parameters of long-range side-chain interaction potentials from protein crystal data , 1997, J. Comput. Chem..

[7]  B. Rost.  Twilight zone of protein sequence alignments. , 1999, Protein engineering.

[8]  Y. Sugita,et al.  Replica-exchange molecular dynamics method for protein folding , 1999 .

[9]  A. Liwo,et al.  Cumulant-based expressions for the multibody terms for the correlation between local and electrostatic interactions in the united-residue force field , 2001 .

[10]  J. Skolnick,et al.  A new combination of replica exchange Monte Carlo and histogram analysis for protein folding and thermodynamics , 2001 .

[11]  C Venclovas,et al.  Comparison of performance in successive CASP experiments , 2001, Proteins.

[12]  Adam Liwo,et al.  Energy‐based reconstruction of a protein backbone from its α‐carbon trace by a Monte‐Carlo method , 2002, J. Comput. Chem..

[13]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[14]  Adam Zemla,et al.  LGA: a method for finding 3D similarities in protein structures , 2003, Nucleic Acids Res..

[15]  A. Liwo,et al.  Addition of side chains to a known backbone with defined side-chain centroids. , 2002, Biophysical chemistry.

[16]  P. Bourne.  CASP and CAFASP experiments and their findings. , 2003, Methods of biochemical analysis.

[17]  D. Case,et al.  Exploring protein native states and large‐scale conformational changes with a modified generalized born model , 2004, Proteins.

[18]  J. Skolnick,et al.  Automated structure prediction of weakly homologous proteins on a genomic scale. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Yang Zhang,et al.  Scoring function for automated assessment of protein structure template quality , 2004, Proteins.

[20]  Yang Zhang,et al.  SPICKER: A clustering approach to identify near‐native protein folds , 2004, J. Comput. Chem..

[21]  J. Janin.  Assessing predictions of protein–protein interaction: The CAPRI experiment , 2005, Protein science : a publication of the Protein Society.

[22]  John Moult,et al.  A decade of CASP: progress, bottlenecks and prognosis in protein structure prediction. , 2005, Current opinion in structural biology.

[23]  J. Hentz,et al.  The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice , 2008, Breast cancer : basic and clinical research.

[24]  Torsten Schwede,et al.  Assessment of CASP7 predictions for template‐based modeling targets , 2007, Proteins.

[25]  A. Liwo,et al.  Modification and optimization of the united-residue (UNRES) potential energy function for canonical simulations. I. Temperature dependence of the effective energy function and tests of the optimization method with single training proteins. , 2007, The journal of physical chemistry. B.

[26]  J. Skolnick,et al.  Erratum: Scoring function for automated assessment of protein structure template quality (Proteins: Structure, Function and Genetics (2004) 57, (702-710)) , 2007 .

[27]  C A Floudas,et al.  Computational methods in protein structure prediction. , 2007, Biotechnology and bioengineering.

[28]  J. Skolnick,et al.  Ab initio protein structure prediction using chunk-TASSER. , 2007, Biophysical journal.

[29]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[30]  Yang Zhang.  Progress and challenges in protein structure prediction. , 2008, Current opinion in structural biology.

[31]  Christopher M. Summa,et al.  Solvent dramatically affects protein structure refinement , 2008, Proceedings of the National Academy of Sciences.

[32]  Yaoqi Zhou,et al.  Specific interactions for ab initio folding of protein terminal regions with secondary structures , 2008, Proteins.

[33]  A. Liwo,et al.  Simulation of Protein Structure and Dynamics with the Coarse-Grained UNRES Force Field , 2008 .

[34]  Christodoulos A Floudas,et al.  Selecting high quality protein structures from diverse conformational ensembles. , 2009, Biophysical journal.

[35]  Adam Liwo,et al.  Exploring the parameter space of the coarse‐grained UNRES force field by random search: Selecting a transferable medium‐resolution force field , 2009, J. Comput. Chem..

[36]  C. Floudas,et al.  Towards accurate residue–residue hydrophobic contact prediction for α helical proteins via integer linear optimization , 2009, Proteins.

[37]  K. Dill,et al.  Assessment of the protein‐structure refinement category in CASP8 , 2009, Proteins.

[38]  Jeffrey Skolnick,et al.  Protein structure prediction by pro-Sp3-TASSER. , 2009, Biophysical journal.

[39]  A. Liwo,et al.  Application of Multiplexed Replica Exchange Molecular Dynamics to the UNRES Force Field: Tests with alpha and alpha+beta Proteins. , 2009, Journal of chemical theory and computation.

[40]  E. Callaway.  Mutation-prediction software rewarded , 2010 .

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

[42]  C. Floudas,et al.  Contact prediction for beta and alpha‐beta proteins using integer linear optimization and its impact on the first principles 3D structure prediction method ASTRO‐FOLD , 2010, Proteins.

[43]  Adrien Treuille,et al.  Predicting protein structures with a multiplayer online game , 2010, Nature.

[44]  Michael Levitt,et al.  Consistent refinement of submitted models at CASP using a knowledge‐based potential , 2010, Proteins.

[45]  Anthony Nicholls,et al.  The SAMPL2 blind prediction challenge: introduction and overview , 2010, J. Comput. Aided Mol. Des..

[46]  R. Dror,et al.  Improved side-chain torsion potentials for the Amber ff99SB protein force field , 2010, Proteins.

[47]  Jianlin Cheng,et al.  APOLLO: a quality assessment service for single and multiple protein models , 2011, Bioinform..

[48]  J. Skolnick,et al.  GOAP: a generalized orientation-dependent, all-atom statistical potential for protein structure prediction. , 2011, Biophysical journal.

[49]  Jens Meiler,et al.  ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. , 2011, Methods in enzymology.

[50]  Z. Popovic,et al.  Crystal structure of a monomeric retroviral protease solved by protein folding game players , 2011, Nature Structural &Molecular Biology.

[51]  Krzysztof Fidelis,et al.  CASP9 results compared to those of previous casp experiments , 2011, Proteins.

[52]  A. Tramontano,et al.  Critical assessment of methods of protein structure prediction (CASP)—round IX , 2011, Proteins.

[53]  Christodoulos A. Floudas,et al.  CONCORD: a consensus method for protein secondary structure prediction via mixed integer linear optimization , 2012, Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences.

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

[55]  C. Floudas,et al.  b-sheet Topology Prediction with High Precision and Recall for b and Mixed a / b Proteins , 2012 .

[56]  K. Dill,et al.  The Protein-Folding Problem, 50 Years On , 2012, Science.

[57]  C. Floudas,et al.  β-sheet Topology Prediction with High Precision and Recall for β and Mixed α/β Proteins , 2012, PloS one.

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

[59]  Daniel W. A. Buchan,et al.  A large-scale evaluation of computational protein function prediction , 2013, Nature Methods.

[60]  Ieee Staff.  2013 IEEE International Conference on Cluster Computing, CLUSTER 2013, Indianapolis, IN, USA, September 23-27, 2013 , 2013, CLUSTER.

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

[62]  Adam K. Sieradzan,et al.  Lessons from application of the UNRES force field to predictions of structures of CASP10 targets , 2013, Proceedings of the National Academy of Sciences.

[63]  Raquell Holmes,et al.  The WeFold gateway: Enabling large-scale science coopetition , 2013, 2013 IEEE International Conference on Cluster Computing (CLUSTER).

[64]  Krzysztof Fidelis,et al.  CASP prediction center infrastructure and evaluation measures in CASP10 and CASP ROLL , 2014, Proteins.

[65]  Hongjun Bai,et al.  Assessment of template‐free modeling in CASP10 and ROLL , 2014, Proteins.

[66]  George A. Khoury,et al.  Protein folding and de novo protein design for biotechnological applications. , 2014, Trends in biotechnology.

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

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

[69]  Anna Tramontano,et al.  Critical assessment of methods of protein structure prediction (CASP) — round x , 2014, Proteins.

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