21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Accelerated Molecular Dynamics Simulations with the AMOEBA Polarizable Force Field on Graphics Processing Units

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The accelerated molecular dynamics (aMD) method has recently been shown to enhance the sampling of biomolecules in molecular dynamics (MD) simulations, often by several orders of magnitude. Here, we describe an implementation of the aMD method for the OpenMM application layer that takes full advantage of graphics processing units (GPUs) computing. The aMD method is shown to work in combination with the AMOEBA polarizable force field (AMOEBA-aMD), allowing the simulation of long time-scale events with a polarizable force field. Benchmarks are provided to show that the AMOEBA-aMD method is efficiently implemented and produces accurate results in its standard parametrization. For the BPTI protein, we demonstrate that the protein structure described with AMOEBA remains stable even on the extended time scales accessed at high levels of accelerations. For the DNA repair metalloenzyme endonuclease IV, we show that the use of the AMOEBA force field is a significant improvement over fixed charged models for describing the enzyme active-site. The new AMOEBA-aMD method is publicly available ( http://wiki.simtk.org/openmm/VirtualRepository) and promises to be interesting for studying complex systems that can benefit from both the use of a polarizable force field and enhanced sampling.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Escaping free-energy minima

          We introduce a novel and powerful method for exploring the properties of the multidimensional free energy surfaces of complex many-body systems by means of a coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates.A characteristic feature of this dynamics is the presence of a history-dependent potential term that, in time, fills the minima in the free energy surface, allowing the efficient exploration and accurate determination of the free energy surface as a function of the collective coordinates. We demonstrate the usefulness of this approach in the case of the dissociation of a NaCl molecule in water and in the study of the conformational changes of a dialanine in solution.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Current status of the AMOEBA polarizable force field.

            Molecular force fields have been approaching a generational transition over the past several years, moving away from well-established and well-tuned, but intrinsically limited, fixed point charge models toward more intricate and expensive polarizable models that should allow more accurate description of molecular properties. The recently introduced AMOEBA force field is a leading publicly available example of this next generation of theoretical model, but to date, it has only received relatively limited validation, which we address here. We show that the AMOEBA force field is in fact a significant improvement over fixed charge models for small molecule structural and thermodynamic observables in particular, although further fine-tuning is necessary to describe solvation free energies of drug-like small molecules, dynamical properties away from ambient conditions, and possible improvements in aromatic interactions. State of the art electronic structure calculations reveal generally very good agreement with AMOEBA for demanding problems such as relative conformational energies of the alanine tetrapeptide and isomers of water sulfate complexes. AMOEBA is shown to be especially successful on protein-ligand binding and computational X-ray crystallography where polarization and accurate electrostatics are critical.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Systematic Validation of Protein Force Fields against Experimental Data

              Molecular dynamics simulations provide a vehicle for capturing the structures, motions, and interactions of biological macromolecules in full atomic detail. The accuracy of such simulations, however, is critically dependent on the force field—the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. Here we present a systematic and extensive evaluation of eight different protein force fields based on comparisons of experimental data with molecular dynamics simulations that reach a previously inaccessible timescale. First, through extensive comparisons with experimental NMR data, we examined the force fields' abilities to describe the structure and fluctuations of folded proteins. Second, we quantified potential biases towards different secondary structure types by comparing experimental and simulation data for small peptides that preferentially populate either helical or sheet-like structures. Third, we tested the force fields' abilities to fold two small proteins—one α-helical, the other with β-sheet structure. The results suggest that force fields have improved over time, and that the most recent versions, while not perfect, provide an accurate description of many structural and dynamical properties of proteins.
                Bookmark

                Author and article information

                Journal
                J Chem Theory Comput
                J Chem Theory Comput
                ct
                jctcce
                Journal of Chemical Theory and Computation
                American Chemical Society
                1549-9618
                1549-9626
                15 October 2013
                12 November 2013
                : 9
                : 11
                : 4684-4691
                Affiliations
                []Department of Pharmacology, University of California San Diego , La Jolla, California 92093United States
                []Center for Theoretical Biological Physics, La Jolla, California 92093United States
                [§ ]Howard Hughes Medical Institute, University of California San Diego , La Jolla, California 92093United States
                []Department of Bioengineering, Stanford University , Stanford, California 94305, United States
                []Department of Chemistry & Biochemistry, NSF Center for Theoretical Biological Physics, National Biomedical Computation Resource, University of California San Diego , La Jolla, California 92093, United States
                Author notes
                [* ]Phone: 858-534-2913. Fax: 858-534-4974. E-mail: slindert@ 123456ucsd.edu .
                Article
                10.1021/ct400514p
                3948463
                24634618
                92892a79-073d-44d4-9075-995bdd8c6ff9
                Copyright © 2013 American Chemical Society
                History
                : 17 June 2013
                Funding
                National Institutes of Health, United States
                Categories
                Article
                Custom metadata
                ct400514p
                ct-2013-00514p

                Computational chemistry & Modeling
                Computational chemistry & Modeling

                Comments

                Comment on this article