research-article

Millisecond-scale molecular dynamics simulations on Anton

SC '09: Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis

Article No.: 65, Pages 1 - 11

https://doi.org/10.1145/1654059.1654126

Published: 14 November 2009 Publication History

Abstract

Anton is a recently completed special-purpose supercomputer designed for molecular dynamics (MD) simulations of biomolecular systems. The machine's specialized hardware dramatically increases the speed of MD calculations, making possible for the first time the simulation of biological molecules at an atomic level of detail for periods on the order of a millisecond---about two orders of magnitude beyond the previous state of the art. Anton is now running simulations on a timescale at which many critically important, but poorly understood phenomena are known to occur, allowing the observation of aspects of protein dynamics that were previously inaccessible to both computational and experimental study. Here, we report Anton's performance when executing actual MD simulations whose accuracy has been validated against both existing MD software and experimental observations. We also discuss the manner in which novel algorithms have been coordinated with Anton's co-designed, application-specific hardware to achieve these results.

References

[1]

A. Bhatele, S. Kumar, C. Mei, J. C. Phillips, G. Zheng, and L. V. Kalé. 2008. Overcoming scaling challenges in biomolecular simulations across multiple platforms. In Proc. IEEE Int. Parallel and Distributed Processing Symp. (Miami, FL, 2008).

[2]

K. J. Bowers, E. Chow, H. Xu, R. O. Dror, M. P. Eastwood, B. A. Gregersen, J. L. Klepeis, I. Kolossváry, M. A. Moraes, F. D. Sacerdoti, J. K. Salmon, Y. Shan, and D. E. Shaw. 2006. Scalable algorithms for molecular dynamics simulations on commodity clusters. In Proc. ACM/IEEE Conf. on Supercomputing (Tampa, FL, 2006).

Digital Library

[3]

K. J. Bowers, R. O. Dror, and D. E. Shaw. 2007. Zonal methods for the parallel execution of range-limited N-body problems. J. Comput. Phys. 221 (1), 303--329.

Digital Library

[4]

E. Chow, C. A. Rendleman, K. J. Bowers, R. O. Dror, D. H. Hughes, J. Gullingsrud, F. D. Sacerdoti, and D. E. Shaw. 2008. Desmond performance on a cluster of multicore processors. D. E. Shaw Research Technical Report DESRES/TR-2008-01. http://deshawresearch.com.

[5]

R. O. Dror, D. H. Arlow, D. W. Borhani, M. Ø. Jensen, S. Piana, and D. E. Shaw. 2009. Identification of two distinct inactive conformations of the β₂-adrenergic receptor reconciles structural and biochemical observations. Proc. Natl. Acad. Sci. USA 106, 4689--4694.

[6]

D. L. Ensign, P. M. Kasson, and V. S. Pande. 2007. Heterogeneity even at the speed limit of folding: large-scale molecular dynamics study of a fast-folding variant of the villin headpiece. J. Mol. Biol. 374, 806--16.

[7]

U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee, and L. G. Pedersen. 1995. A smooth particle mesh Ewald method. J. Chem. Phys. 103 (19), 8577--8593.

[8]

R. D. Fine, G. Dimmler, and C. Levinthal. 1991. A special purpose, hardwired computer for molecular simulation. Proteins: Struct., Funct., Genet. 11 (4), 242--253.

[9]

B. G. Fitch, A. Rayshubskiy, M. Eleftheriou, T. J. C. Ward, M. E. Giampapa, M. C. Pitman, J. W. Pitera, W. C. Swope, and R. S. Germain. 2006. Blue Matter: approaching the limits of concurrency for classical molecular dynamics. In Proc. ACM/IEEE Conf. on Supercomputing (Tampa, FL, 2006).

Digital Library

[10]

P. L. Freddolino, F. Liu, M. H. Gruebele, and K. Schulten. 2008. Ten-microsecond MD simulation of a fast-folding WW domain. Biophys. J. 94 (10), L75--L77.

[11]

R. S. Germain, B. Fitch, A. Rayshubskiy, M. Eleftheriou, M. C. Pitman, F. Suits, M. Giampapa, and T. J. C. Ward. 2005. Blue Matter on Blue Gene/L: massively parallel computation for biomolecular simulation. In Proc. 3rd IEEE/ACM/IFIP Int. Conf. on Hardware/Software Codesign and System Synthesis (New York, NY, 2005).

Digital Library

[12]

A. Grossfield, M. C. Pitman, S. E. Feller, O. Soubias, and K. Gawrisch. 2008. Internal hydration increases during activation of the G-protein-coupled receptor rhodopsin. J. Mol. Biol. 381, 478--486.

[13]

J. B. Hall and D. Fushman. 2006. Variability of the 15N chemical shielding tensors in the B3 domain of protein G from 15N relaxation measurements at several fields. Implications for backbone order parameters. J. Am. Chem. Soc. 128 (24), 7855--7870.

[14]

B. Hess, C. Kutzner, D. van der Spoel, and E. Lindahl. 2008. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4 (2), 435--447.

[15]

R. W. Hockney and J. W. Eastwood. 1988. Computer Simulation Using Particles. Adam Hilger, Bristol, England, 1988.

Digital Library

[16]

H. W. Horn, W. C. Swope, J. W. Pitera, J. D. Madura, T. J. Dick, G. L. Hura, and T. Head-Gordon. 2004. Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew. J. Chem. Phys. 120 (20), 9665--9678.

[17]

V. Hornak, R. Abel, A. Okur, B. Strockbine, A. Roitberg, and C. Simmerling. 2006. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins: Struct., Funct., Bioinf. 65, 712--725.

[18]

W. L. Jorgensen, D. S. Maxwell, and J. Tirado-Rives. 1996. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 118 (45), 11225--11236.

[19]

L. V. Kalé, R. Skeel, M. Bhandarkar, R. Brunner, A. Gursoy, N. Krawetz, J. Phillips, A. Shinozaki, K. Varadarajan, and K. Schulten. 1999. NAMD2: greater scalability for parallel molecular dynamics. J. Comput. Phys. 151 (1), 283--312.

Digital Library

[20]

F. Khalili-Araghi, J. Gumbart, P.-C. Wen, M. Sotomayor, E. Tajkhorshid, and K. Shulten. 2009. Molecular dynamics simulations of membrane channels and transporters. Curr. Opin. Struct. Biol. 19 (2), 128--137.

[21]

J. L. Klepeis, K. Lindorff-Larsen, R. O. Dror, and D. E. Shaw. 2009. Long-timescale molecular dynamics simulations of protein structure and function. Curr. Opin. Struct. Biol. 19 (2), 120--127.

[22]

J. S. Kuskin, C. Young, J. P. Grossman, B. Batson, M. Deneroff, R. O. Dror, and D. E. Shaw. 2008. Incorporating flexibility in Anton, a specialized machine for molecular dynamics simulation. In Proc. 14th Int. Symp. on High-Performance Computer Architecture (Salt Lake City, UT, 2008).

[23]

R. H. Larson, J. K. Salmon, R. O. Dror, M. M. Deneroff, C. Young, J. P. Grossman, Y. Shan, J. L. Klepeis, and D. E. Shaw. 2008. High-throughput pairwise point interactions in Anton, a specialized machine for molecular dynamics simulation. In Proc. 14th Int. Symp. on High-Performance Computer Architecture (Salt Lake City, UT, 2008).

[24]

P. Maragakis, K. Lindorff-Larsen, M. Eastwood, R. O. Dror, J. L. Klepeis, I. T. Arkin, M. Ø. Jensen, H. Xu, N. Trbovic, R. A. Friesner, A. G. Palmer III, and D. E. Shaw. 2008. Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins. J. Phys. Chem. B 112, 6155--6158.

[25]

K. Martinez-Mayorga, M. C. Pitman, A. Grossfield, S. E. Feller, and M. F. Brown. 2006. Retinal counterion switch mechanism in vision evaluated by molecular simulations. J. Am. Chem. Soc. 128, 16502--16503.

[26]

J. A. McCammon, B. R. Gelin, and M. Karplus. 1977. Dynamics of folded proteins. Nature 267, 585--590.

[27]

T. Narumi, Y. Ohno, N. Okimoto, T. Koishi, A. Suenaga, N. Futasugi, R. Yanai, R. Himeno, S. Fujikawa, M. Taiji, and M. Ikei. 2006. A 55 TFLOPS simulation of amyloid-forming peptides from yeast prion Sup35 with the special-purpose computer system MDGRAPE-3. In Proc. ACM/IEEE Conf. on Supercomputing (Tampa, FL, 2006).

Digital Library

[28]

S. Piana-Agostinetti, K. Lindorff-Larsen, P. Maragakis, M. P. Eastwood, R. O. Dror, and D. E. Shaw. 2009. Improving molecular mechanics force fields by comparison of microsecond simulations with NMR experiments. Biophys. J. 96 (3), 406a.

[29]

S. J. Plimpton, S. Attaway, B. Hendrickson, J. Swegle, C. Vaughan, and D. Gardner. 1996. Transient dynamics simulations: parallel algorithms for contact detection and smoothed particle hydrodynamics. In Proc. ACM/IEEE Conf. on Supercomputing (Pittsburgh, PA, 1996).

Digital Library

[30]

B. Roux. 2007. A proton-controlled check valve for sodium ion transport. Nature Chem. Bio. 3, 609--610.

[31]

Y. Shan, J. L. Klepeis, M. P. Eastwood, R. O. Dror, and D. E. Shaw. 2005. Gaussian split Ewald: a fast Ewald mesh method for molecular simulation. J. Chem. Phys. 122, 054101.

[32]

D. E. Shaw. A fast, scalable method for the parallel evaluation of distance-limited pairwise particle interactions. 2005. J. Comput. Chem. 26 (13), 1318--1328.

[33]

D. E. Shaw, M. M. Deneroff, R. O. Dror, J. S. Kuskin, R. H. Larson, J. K. Salmon, C. Young, B. Batson, K. J. Bowers, J. C. Chao, M. P. Eastwood, J. Gagliardo, J. P. Grossman, C. R. Ho, D. J. Ierardi, I. Kolossváry, J. L. Klepeis, T. Layman, C. McLeavey, M. A. Moraes, R. Mueller, E. C. Priest, Y. Shan, J. Spengler, M. Theobald, B. Towles, and S. C. Wang. 2007. Anton: a special-purpose machine for molecular dynamics simulation. In Proc. 34th Int. Symp. on Computer Architecture (San Diego, CA, 2007). ACM Press, New York, NY, 1--12.

Digital Library

[34]

R. D. Skeel. 1999. Symplectic integration with floating-point arithmetic and other approximations. In Proc. NSF/CBMS Regional Conf. on Numerical Analysis of Hamiltonian Differential Equations (Golden, CO, 1999) 29, 3--18.

Digital Library

[35]

A. Suenaga, T. Narumi, N. Futatsugi, R. Yanai, Y. Ohno, N. Okimoto, and M. Taiji. 2007. Folding dynamics of 10-residue b-hairpin peptide chignolin. Chem. Asian J. 2, 591--598.

[36]

C. Young, J. A. Bank, R. O. Dror, J. P. Grossman, J. K. Salmon, and D. E. Shaw. 2009. A 32x32x32, spatially distributed 3D FFT in four microseconds on Anton. In Proc. ACM/IEEE Conf. on Supercomputing (Portland, OR, 2009).

Digital Library

[37]

R. Zhou, E. Harder, H. Xu, and B. J. Berne. 2001. Efficient multiple time step method for use with Ewald and particle mesh Ewald for large biomolecular systems. J. Chem. Phys. 115 (5), 2348--2358.

Cited By

Chen JPotlapalli RQuan HChen LXie YPouriyeh SSakib NLiu LXie Y(2024)Exploring DNA Damage and Repair Mechanisms: A Review with Computational InsightsBioTech10.3390/biotech1301000313:1(3)Online publication date: 16-Jan-2024
https://doi.org/10.3390/biotech13010003
Sasidharan AEvans KSchenk O(2024)Parallel Algorithms for Intersection ComputationProceedings of the Platform for Advanced Scientific Computing Conference10.1145/3659914.3659929(1-11)Online publication date: 3-Jun-2024
https://dl.acm.org/doi/10.1145/3659914.3659929
Wu FHuang YYang GYe SMukamel SJiang J(2024)Unraveling dynamic protein structures by two-dimensional infrared spectra with a pretrained machine learning modelProceedings of the National Academy of Sciences10.1073/pnas.2409257121121:27Online publication date: 25-Jun-2024
https://doi.org/10.1073/pnas.2409257121
Show More Cited By

Index Terms

Recommendations

Millisecond-scale molecular dynamics simulations on Anton
SC '09: Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis

Anton is a recently completed special-purpose supercomputer designed for molecular dynamics (MD) simulations of biomolecular systems. The machine's specialized hardware dramatically increases the speed of MD calculations, making possible for the first ...
Anton, a special-purpose machine for molecular dynamics simulation

The ability to perform long, accurate molecular dynamics (MD) simulations involving proteins and other biological macro-molecules could in principle provide answers to some of the most important currently outstanding questions in the fields of biology, ...
Massively parallel molecular dynamics simulations of lysozyme unfolding

We have performed molecular dynamics simulations for a total duration of more than 10 µs (with most molecular trajectories being 1 µs in duration) to study, the effect of a single mutation on hen lysozyme protein stability and denaturing, using an IBM ...

Comments

Information & Contributors

Information

Published In

cover image ACM Conferences

SC '09: Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis

November 2009

778 pages

ISBN:9781605587448

DOI:10.1145/1654059

Conference Chair:
Wilfred Pinfold

Copyright © 2009 ACM.

Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

Sponsors

SIGARCH: ACM Special Interest Group on Computer Architecture
IEEE-CS: Computer Society

Publisher

Association for Computing Machinery

New York, NY, United States

Publication History

Published: 14 November 2009

Permissions

Request permissions for this article.

Request Permissions

Check for updates

Qualifiers

Research-article

Conference

SC '09

Sponsor:

SIGARCH
IEEE-CS

SC '09: International Conference for High Performance Computing, Networking, Storage and Analysis

November 14 - 20, 2009

Oregon, Portland

Acceptance Rates

SC '09 Paper Acceptance Rate 59 of 261 submissions, 23%;

Overall Acceptance Rate 1,516 of 6,373 submissions, 24%

Contributors

Other Metrics

View Article Metrics

Bibliometrics & Citations

Bibliometrics

Article Metrics

206
Total Citations
View Citations
774
Total Downloads

Downloads (Last 12 months)214
Downloads (Last 6 weeks)31

Reflects downloads up to 23 Oct 2024

Other Metrics

View Author Metrics

Citations

Cited By

Chen JPotlapalli RQuan HChen LXie YPouriyeh SSakib NLiu LXie Y(2024)Exploring DNA Damage and Repair Mechanisms: A Review with Computational InsightsBioTech10.3390/biotech1301000313:1(3)Online publication date: 16-Jan-2024
https://doi.org/10.3390/biotech13010003
Sasidharan AEvans KSchenk O(2024)Parallel Algorithms for Intersection ComputationProceedings of the Platform for Advanced Scientific Computing Conference10.1145/3659914.3659929(1-11)Online publication date: 3-Jun-2024
https://dl.acm.org/doi/10.1145/3659914.3659929
Wu FHuang YYang GYe SMukamel SJiang J(2024)Unraveling dynamic protein structures by two-dimensional infrared spectra with a pretrained machine learning modelProceedings of the National Academy of Sciences10.1073/pnas.2409257121121:27Online publication date: 25-Jun-2024
https://doi.org/10.1073/pnas.2409257121
Nencini RTempra CBiriukov DRiopedre-Fernandez MCruces Chamorro VPolák JMason POndo DHeyda JOllila OJungwirth PJavanainen MMartinez-Seara H(2024)Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The prosECCo75 Biomolecular Force FieldJournal of Chemical Theory and Computation10.1021/acs.jctc.4c0074320:17(7546-7559)Online publication date: 26-Aug-2024
https://doi.org/10.1021/acs.jctc.4c00743
Strand ETourlomousis FGershenfeld N(2024)Mesoscale material modeling with memoryless isotropic point particlesJournal of Computational Science10.1016/j.jocs.2023.10219875(102198)Online publication date: Jan-2024
https://doi.org/10.1016/j.jocs.2023.102198
Sinha MPandit SSingh PChauhan SParthasarathi R(2024)Visualizing chemical functionality and structural insights into SARS-CoV-2 proteinsStem Cells10.1016/B978-0-323-95545-4.00007-4(257-275)Online publication date: 2024
https://doi.org/10.1016/B978-0-323-95545-4.00007-4
Li JZhao TGuo ZShi SLiu LTan GJia WYuan GWang ZMohror KArnold DBadia R(2023)Enhance the Strong Scaling of LAMMPS on FugakuProceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis10.1145/3581784.3607064(1-13)Online publication date: 12-Nov-2023
https://dl.acm.org/doi/10.1145/3581784.3607064
Damjanovic JLin YMurphy J(2023)Modeling Changes in Molecular Dynamics Time Series as Wasserstein Barycentric Interpolations2023 International Conference on Sampling Theory and Applications (SampTA)10.1109/SampTA59647.2023.10301374(1-7)Online publication date: 10-Jul-2023
https://doi.org/10.1109/SampTA59647.2023.10301374
Sheng NTong ZJiang CMa XYang XLi HTian ZZhang Q(2023)Microsecond Simulation in a Special-Purpose Molecular Dynamics Computer Cluster2023 11th International Conference on Bioinformatics and Computational Biology (ICBCB)10.1109/ICBCB57893.2023.10246549(151-157)Online publication date: 21-Apr-2023
https://doi.org/10.1109/ICBCB57893.2023.10246549
Zaka AYousaf MShahzad SRao HFoo JSiddiqi S(2023) Structural and functional insights into a novel homozygous missense pathogenic variant in CUL7 identified in consanguineous Pakistani family Journal of Biomolecular Structure and Dynamics10.1080/07391102.2023.222488942:10(5092-5103)Online publication date: 22-Jun-2023
https://doi.org/10.1080/07391102.2023.2224889
Show More Cited By

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Full Access

Get this Publication

View options

PDF

View or Download as a PDF file.

eReader

View online with eReader.

Media

Figures

Other

Tables

View Table of Contents