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Scott M. Le Grand

Bio: Scott M. Le Grand is an academic researcher from Amazon.com. The author has contributed to research in topics: Sorting algorithm & Thread (computing). The author has an hindex of 15, co-authored 27 publications receiving 5691 citations. Previous affiliations of Scott M. Le Grand include University of California, Los Angeles & Pennsylvania State University.

Papers
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Journal ArticleDOI
TL;DR: An implementation of explicit solvent all atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA-enabled GPUs, providing results that are statistically indistinguishable from the traditional CPU version of the software and with performance that exceeds that achievable by the CPUs running on all conventional CPU-based clusters and supercomputers.
Abstract: We present an implementation of explicit solvent all atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA-enabled GPUs. First released publicly in April 2010 as part of version 11 of the AMBER MD package and further improved and optimized over the last two years, this implementation supports the three most widely used statistical mechanical ensembles (NVE, NVT, and NPT), uses particle mesh Ewald (PME) for the long-range electrostatics, and runs entirely on CUDA-enabled NVIDIA graphics processing units (GPUs), providing results that are statistically indistinguishable from the traditional CPU version of the software and with performance that exceeds that achievable by the CPU version of AMBER software running on all conventional CPU-based clusters and supercomputers. We briefly discuss three different precision models developed specifically for this work (SPDP, SPFP, and DPDP) and highlight the technical details of the approach as it extends beyond previously reported work [Gotz et al., J. Chem. Theory Comput. 2012, DOI: 10.1021/ct200909j; Le Grand et al., Comp. Phys. Comm. 2013, DOI: 10.1016/j.cpc.2012.09.022].We highlight the substantial improvements in performance that are seen over traditional CPU-only machines and provide validation of our implementation and precision models. We also provide evidence supporting our decision to deprecate the previously described fully single precision (SPSP) model from the latest release of the AMBER software package.

2,418 citations

Journal ArticleDOI
TL;DR: An implementation of generalized Born implicit solvent all-atom classical molecular dynamics within the AMBER program package that runs entirely on CUDA enabled NVIDIA graphics processing units (GPUs) and shows performance that is on par with, and in some cases exceeds, that of traditional supercomputers.
Abstract: We present an implementation of generalized Born implicit solvent all-atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA enabled NVIDIA graphics processing units (GPUs). We discuss the algorithms that are used to exploit the processing power of the GPUs and show the performance that can be achieved in comparison to simulations on conventional CPU clusters. The implementation supports three different precision models in which the contributions to the forces are calculated in single precision floating point arithmetic but accumulated in double precision (SPDP), or everything is computed in single precision (SPSP) or double precision (DPDP). In addition to performance, we have focused on understanding the implications of the different precision models on the outcome of implicit solvent MD simulations. We show results for a range of tests including the accuracy of single point force evaluations and energy conservation as well as structural properties pertainining to protein dynamics. The numerical noise due to rounding errors within the SPSP precision model is sufficiently large to lead to an accumulation of errors which can result in unphysical trajectories for long time scale simulations. We recommend the use of the mixed-precision SPDP model since the numerical results obtained are comparable with those of the full double precision DPDP model and the reference double precision CPU implementation but at significantly reduced computational cost. Our implementation provides performance for GB simulations on a single desktop that is on par with, and in some cases exceeds, that of traditional supercomputers.

1,645 citations

Book
02 Apr 2012
TL;DR: This work Modeling Side Chains in Peptides and Proteins with the Locally Enhanced Sampling/Simulated Annealing Method and the Role of Interior Side-Chain Packing in Protein Folding and Stability are presented.
Abstract: 1 Modeling Side Chains in Peptides and Proteins with the Locally Enhanced Sampling/Simulated Annealing Method.- 2 Conformation Searching Using Simulated Annealing.- 3 Multiple-Start Monte Carlo Docking of Flexible Ligands.- 4 The Genetic Algorithm and Protein Tertiary Structure Prediction.- 5 Conformational Search and Protein Folding.- 6 Building Protein Folds Using Distance Geometry: Towards a General Modeling and Prediction Method.- 7 Molecular Dynamics Studies of Protein and Peptide Folding and Unfolding.- 8 Contact Potential for Global Identification of Correct Protein Folding.- 9 Neural Networks for Molecular Sequence Classification.- 10 The "Dead-End Elimination" Theorem: A New Approach to the Side-Chain Packing Problem.- 11 Short Structural Motifs: Definition, Identification, and Applications.- 12 In Search of Protein Folds.- 13 An Adaptive Branch-and-Bound Minimization Method Based on Dynamic Programming.- 14 Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox.- 15 Toward Quantitative Protein Structure Prediction.- 16 The Role of Interior Side-Chain Packing in Protein Folding and Stability.- Keyword Index.

912 citations

Journal ArticleDOI
TL;DR: This precision model replaces double precision arithmetic with fixed point integer arithmetic for the accumulation of force components as compared to a previously introduced model that uses mixed single/double precision arithmetic, which significantly boosts performance on modern GPU hardware without sacrificing numerical accuracy.

851 citations

Journal ArticleDOI
TL;DR: Since no significant difference in kinetics or thermodynamics is observed by the use of fast HMR trajectories, further evidence is provided that long-time-step HMR MD simulations are a viable tool for accelerating molecular dynamics simulations for molecules of biochemical interest.
Abstract: Previous studies have shown that the method of hydrogen mass repartitioning (HMR) is a potentially useful tool for accelerating molecular dynamics (MD) simulations. By repartitioning the mass of heavy atoms into the bonded hydrogen atoms, it is possible to slow the highest-frequency motions of the macromolecule under study, thus allowing the time step of the simulation to be increased by up to a factor of 2. In this communication, we investigate further how this mass repartitioning allows the simulation time step to be increased in a stable fashion without significantly increasing discretization error. To this end, we ran a set of simulations with different time steps and mass distributions on a three-residue peptide to get a comprehensive view of the effect of mass repartitioning and time step increase on a system whose accessible phase space is fully explored in a relatively short amount of time. We next studied a 129-residue protein, hen egg white lysozyme (HEWL), to verify that the observed behavior extends to a larger, more-realistic, system. Results for the protein include structural comparisons from MD trajectories, as well as comparisons of pKa calculations via constant-pH MD. We also calculated a potential of mean force (PMF) of a dihedral rotation for the MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)methanethiosulfonate] spin label via umbrella sampling with a set of regular MD trajectories, as well as a set of mass-repartitioned trajectories with a time step of 4 fs. Since no significant difference in kinetics or thermodynamics is observed by the use of fast HMR trajectories, further evidence is provided that long-time-step HMR MD simulations are a viable tool for accelerating MD simulations for molecules of biochemical interest.

771 citations


Cited by
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01 May 1993
TL;DR: Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems.
Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

29,323 citations

Journal ArticleDOI
TL;DR: In this paper, the potential energy surface is transformed into a collection of interpenetrating staircases, and the lowest known structures are located for all Lennard-Jones clusters up to 110 atoms, including a number that have never been found before in unbiased searches.
Abstract: We describe a global optimization technique using “basin-hopping” in which the potential energy surface is transformed into a collection of interpenetrating staircases. This method has been designed to exploit the features that recent work suggests must be present in an energy landscape for efficient relaxation to the global minimum. The transformation associates any point in configuration space with the local minimum obtained by a geometry optimization started from that point, effectively removing transition state regions from the problem. However, unlike other methods based upon hypersurface deformation, this transformation does not change the global minimum. The lowest known structures are located for all Lennard-Jones clusters up to 110 atoms, including a number that have never been found before in unbiased searches.

2,637 citations

Journal ArticleDOI
TL;DR: An implementation of explicit solvent all atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA-enabled GPUs, providing results that are statistically indistinguishable from the traditional CPU version of the software and with performance that exceeds that achievable by the CPUs running on all conventional CPU-based clusters and supercomputers.
Abstract: We present an implementation of explicit solvent all atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA-enabled GPUs. First released publicly in April 2010 as part of version 11 of the AMBER MD package and further improved and optimized over the last two years, this implementation supports the three most widely used statistical mechanical ensembles (NVE, NVT, and NPT), uses particle mesh Ewald (PME) for the long-range electrostatics, and runs entirely on CUDA-enabled NVIDIA graphics processing units (GPUs), providing results that are statistically indistinguishable from the traditional CPU version of the software and with performance that exceeds that achievable by the CPU version of AMBER software running on all conventional CPU-based clusters and supercomputers. We briefly discuss three different precision models developed specifically for this work (SPDP, SPFP, and DPDP) and highlight the technical details of the approach as it extends beyond previously reported work [Gotz et al., J. Chem. Theory Comput. 2012, DOI: 10.1021/ct200909j; Le Grand et al., Comp. Phys. Comm. 2013, DOI: 10.1016/j.cpc.2012.09.022].We highlight the substantial improvements in performance that are seen over traditional CPU-only machines and provide validation of our implementation and precision models. We also provide evidence supporting our decision to deprecate the previously described fully single precision (SPSP) model from the latest release of the AMBER software package.

2,418 citations

Journal ArticleDOI
TL;DR: The most recent developments, since version 9 was released in April 2006, of the Amber and AmberTools MD software packages are outlined, referred to here as simply the Amber package.
Abstract: Molecular dynamics (MD) allows the study of biological and chemical systems at the atomistic level on timescales from femtoseconds to milliseconds. It complements experiment while also offering a way to follow processes difficult to discern with experimental techniques. Numerous software packages exist for conducting MD simulations of which one of the widest used is termed Amber. Here, we outline the most recent developments, since version 9 was released in April 2006, of the Amber and AmberTools MD software packages, referred to here as simply the Amber package. The latest release represents six years of continued development, since version 9, by multiple research groups and the culmination of over 33 years of work beginning with the first version in 1979. The latest release of the Amber package, version 12 released in April 2012, includes a substantial number of important developments in both the scientific and computer science arenas. We present here a condensed vision of what Amber currently supports and where things are likely to head over the coming years. Figure 1 shows the performance in ns/day of the Amber package version 12 on a single-core AMD FX-8120 8-Core 3.6GHz CPU, the Cray XT5 system, and a single GPU GTX680. © 2012 John Wiley & Sons, Ltd.

1,734 citations

Patent
Leonard G. Presta1
14 Jan 2000
TL;DR: In this article, the present invention concerns polypeptides comprising a variant of the Fc region, which have altered effector function as a consequence of one or more amino acid modifications in the region thereof.
Abstract: The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

1,596 citations