A Flexible, Grid-Enabled Web Portal for GROMACS Molecular Dynamics Simulations.

Molecular dynamics simulations are becoming a standard part of workflows in structural biology. They are used for tasks as diverse as assessing molecular flexibility, probing conformational changes, assessing the impact of mutations, or gaining information about molecular interactions. However, performing a successful simulation requires sufficient computational resources, familiarity with the simulation software, and experience in the setup of a system and the analysis of the resulting trajectories. These considerations become especially critical in large-scale parametric MD simulations. Offering such tools to a wide user community requires a robust and versatile, but user-friendly, facility for molecular dynamics simulations with access to vast computational resources. Here, we present the GROMACS grid-enabled Web portal for the setup and execution of molecular dynamics simulation on the WeNMR grid infrastructure, a distributed network of computational resources within the European Grid Initiative. The Web portal aims at ease-of-use through automated setup of the simulation system using best-practice protocols, yet allowing for tuning of key parameters. Alternatively, the simulation can be started from preconfigured GROMACS simulation systems. Performing multiple lengthy calculations using multiple processors on the WeNMR grid infrastructure ensures scalability. The combination of analysis routines for quality assurance and automatic recovery in case of failures provides a reliable platform for MD simulations. The GROMACS Web portal is embedded within the services of the WeNMR Virtual Research Community (VRC) accessible from http://www.wenmr.eu/wenmr/nmr-services . It is freely accessible upon registration with a valid X509 personal certificate with the enmr.eu Virtual Organization (VO).

[1]  Tsjerk A. Wassenaar,et al.  The eNMR platform for structural biology , 2010, Journal of Structural and Functional Genomics.

[2]  Haruki Nakamura,et al.  Application of MDGRAPE‐3, a special purpose board for molecular dynamics simulations, to periodic biomolecular systems , 2009, J. Comput. Chem..

[3]  P. P. Ewald.  Die Berechnung optischer und elektrostatischer Gitterpotentiale , 1921 .

[4]  Andrew E. Torda,et al.  The GROMOS biomolecular simulation program package , 1999 .

[5]  Dmitri I. Svergun,et al.  WeNMR: Structural Biology on the Grid , 2011, Journal of Grid Computing.

[6]  D. M. F. Aalten,et al.  PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules , 1996, J. Comput. Aided Mol. Des..

[7]  Ron O Dror,et al.  Identification of two distinct inactive conformations of the β2-adrenergic receptor reconciles structural and biochemical observations , 2009, Proceedings of the National Academy of Sciences.

[8]  Wilfred F. van Gunsteren,et al.  An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase , 2001, J. Comput. Chem..

[9]  Kyle A. Beauchamp,et al.  Molecular simulation of ab initio protein folding for a millisecond folder NTL9(1-39). , 2010, Journal of the American Chemical Society.

[10]  R. Best,et al.  Tackling force-field bias in protein folding simulations: folding of Villin HP35 and Pin WW domains in explicit water. , 2010, Biophysical journal.

[11]  Wilfred F. van Gunsteren,et al.  A generalized reaction field method for molecular dynamics simulations , 1995 .

[12]  Andrea Amadei,et al.  Molecular dynamics simulations with constrained roto-translational motions: Theoretical basis and statistical mechanical consistency , 2000 .

[13]  Holger Gohlke,et al.  The Amber biomolecular simulation programs , 2005, J. Comput. Chem..

[14]  Terry P Lybrand,et al.  Staggered Mesh Ewald: An extension of the Smooth Particle-Mesh Ewald method adding great versatility. , 2009, Journal of chemical theory and computation.

[15]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

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

[17]  TSJERK A. WASSENAAR,et al.  The effect of box shape on the dynamic properties of proteins simulated under periodic boundary conditions , 2006, J. Comput. Chem..

[18]  VINCENT ZOETE,et al.  SwissParam: A fast force field generation tool for small organic molecules , 2011, J. Comput. Chem..

[19]  Peter L. Freddolino,et al.  Molecular dynamics simulations of the complete satellite tobacco mosaic virus. , 2006, Structure.

[20]  Martin N. Rossor,et al.  Advanced online publication. , 2005, Nature structural biology.

[21]  Rahman,et al.  Molecular-dynamics study of atomic motions in water. , 1985, Physical review. B, Condensed matter.

[22]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[23]  C. Woodward,et al.  Structure of form III crystals of bovine pancreatic trypsin inhibitor. , 1987, Journal of molecular biology.

[24]  Jur P. van den Berg,et al.  A method to obtain a near‐minimal‐volume molecular simulation of a macromolecule, using periodic boundary conditions and rotational constraints , 2004, J. Comput. Chem..

[25]  A. Garcia,et al.  Microsecond simulations of the folding/unfolding thermodynamics of the Trp‐cage miniprotein , 2010, Proteins.

[26]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[27]  John L. Klepeis,et al.  Millisecond-scale molecular dynamics simulations on Anton , 2009, Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis.

[28]  D. van der Spoel,et al.  GROMACS: A message-passing parallel molecular dynamics implementation , 1995 .

[29]  R. Dror,et al.  Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins. , 2008, The journal of physical chemistry. B.

[30]  M. Karplus,et al.  Dynamics of folded proteins , 1977, Nature.

[31]  R. Friesner,et al.  Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides† , 2001 .

[32]  Alexander D. MacKerell,et al.  Development and current status of the CHARMM force field for nucleic acids , 2000, Biopolymers.

[33]  M. Parrinello,et al.  Canonical sampling through velocity rescaling. , 2007, The Journal of chemical physics.

[34]  Modesto Orozco,et al.  MDWeb and MDMoby: an integrated web-based platform for molecular dynamics simulations , 2012, Bioinform..

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

[36]  H. Berendsen,et al.  Molecular Dynamics Simulations: Techniques and Approaches , 1984 .

[37]  G L Gilliland,et al.  Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal protein G and comparison with NMR. , 1994, Biochemistry.

[38]  K. Beyreuther,et al.  Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease. , 1995, European journal of biochemistry.

[39]  A. Bonvin,et al.  The HADDOCK web server for data-driven biomolecular docking , 2010, Nature Protocols.

[40]  Pramod C. Nair,et al.  An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0. , 2011, Journal of chemical theory and computation.

[41]  F. J. Luque,et al.  Dynamics of B-DNA on the microsecond time scale. , 2007, Journal of the American Chemical Society.

[42]  P. Kollman,et al.  Automatic atom type and bond type perception in molecular mechanical calculations. , 2006, Journal of molecular graphics & modelling.

[43]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[44]  T. Schlick,et al.  Biomolecular modeling and simulation: a field coming of age , 2011, Quarterly Reviews of Biophysics.