Pittsburgh Supercomputing Center 

Advancing the state-of-the-art in high-performance computing, communications and informatics.

Anton

Anton, named for Anton van Leeuwenhoek, is a special purpose supercomputer for molecular dynamics (MD) simulations, designed and constructed by D. E. Shaw Research (DESRES).   In colllaboration with DESRES, the Biomedical Applications Group at PSC is hosting an Anton machine for general availability to the national biomedical community. 

Anton can carry out MD simulations at an atomic level and on the scale of milliseconds - and at speeds up to 100 times faster than a conventional supercomputer.

The availability of Anton at PSC was made possible through the generosity of D.E. Shaw and grants from the NIH's National Institute of General Medical Sciences.

Access to Anton

Anton is allocated annually with proposals reviewed by a committee convened by the National Research Council at the National Academies. To qualify for an allocation on Anton, the principal investigator (PI) must be a faculty or staff member at a U.S. academic or non-profit research institution.

The deadline to submit proposals for this year was June 16, 2014. Please watch this web site for an announcement of the next proposal submission opportunity.

Anton usage

Anton uses specialized hardware to perform molecular dynamics simulations orders of magnitude faster than general purpose hardware running traditional MD software.

Anton is designed primarily to accelerate classical MD simulations of biomolecular systems with periodic boundary conditions and explicit solvent. Projects that maximize the benefit of Anton to the scientific community focus on questions that will be greatly advanced by multi-microsecond MD simulations, and especially those questions that require long continuous trajectories rather than a sampling of many short ones.

Simulations are standard MD runs in the NVE, NVT (isothermal), and NPT (isothermal, isobaric) ensembles.  They may use Berendsen or Nose-Hoover thermostats, and may use Berendsen or MTK barostats with isotropic or semi-isotropic scaling. Simulation conditions may include the specification of a uniform constant applied electric field. Position restraints, on a per atom basis, are allowed. Enhanced sampling is also available in three basic forms: (i) simulated tempering with the Nose- Hoover thermostat, (ii) application of a restraint between the centers of mass of groups of atoms, and (iii) application of a restraint based on the calculation of RMSD (root mean squared deviation) to atomic positions of a reference structure. The total number of atoms involved in either distance restraints or RMSD restraints may not exceed 2048.

Typically, the simulation cell must have only right angles (i.e., it must be a cubic or orthorhombic box), and must be a minimum of 45 Angstroms on each side.  In most cases, the ratio of the largest side to smallest side must not exceed 1.5:1.

Simulations use recent variants of the following standard biomolecular force fields: CHARMM (e.g., CHARMM22, CHARMM27 - including CMAP corrections, and CHARMM36 for lipids), AMBER (e.g., AMBER99, AMBER99SB, AMBER03), or OPLS (e.g., OPLS-AA/L). Modified versions of the CHARMM and AMBER force fields, based on published research by DESRES, are also acceptable (and available through the simulation setup tools). Water is modeled with the SPC, TIP3P, or TIP4P models, or their variants.

Chemical systems should contain between 20,000 and 150,000 atoms (including solvent atoms), and  typically consist of some combination of protein, DNA, RNA, lipids, water, and standard ions.

Benchmarks

Anton enables scientists to perform MD simulations of biomolecular systems nearly two orders of magnitude faster than the previous state of the art. This table shows benchmark information for a number of systems of various sizes. Performance was measured on a 512-node Anton machine like the one hosted by the PSC. Note that Anton is a single user system, i.e., simulations on Anton use all 512 nodes.

Chemical system (PDB ID) Number of atoms Approximate performance (microseconds/machine-day)*
DHFR (5DFR) 23558 17.4
aSFP (1SFP) 48423 11.7
FtsZ (1FSZ) 98236 5.7
T7Lig (1A01) 116650 5.5

* All simulations used 2.5-femtosecond time steps with long-range interactions evaluated at every other time step and a Berendsen thermostat applied every 100 time steps.

Research conducted on Anton

Listed here is just some of the groundbreaking research enabled by Anton:

Publications

Here is a list of publications for research that made use of Anton at PSC:

2014

  • Adelman JL, Sheng Y, Choe S, Abramson J, Wright EM, Rosenberg JM, Grabe M (2014) Structural determinants of water permeation through the sodium-galactose transporter vSGLT. Biophys J 106(6):1280–1289.
  • Li Q, Wanderling S, Paduch M, Medovoy D, Singharoy A, McGreevy R, Villalba-Galea CA, Hulse RE, Roux B, Schulten K, Kossiakoff A, Perozo E (2014) Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nat Struct Mol Biol 21(3):244–252.
  • Liu Y, Prigozhin MB, Schulten K, Gruebele M(2014) Observation of complete pressure-jump protein refolding in molecular dynamics simulation and experiment. J Am Chem Soc 136(11):4265–4272.
  • Monroe JI, El-Nahal WG, Shirts MR (2014) Investigating the mutation resistance of nonnucleoside inhibitors of HIV-RT using multiple microsecond atomistic simulations. Proteins 82(1):130–144.
  • Provasi D, Negri A, Coller BS, Filizola M (2014) Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multi-microsecond, all-atom molecular dynamics simulations. Proteins, in press.
  • Rui H, Root KT, Lee J, Glover KJ, Im W (2014) Probing the u-shaped conformation of caveolin-1 in a bilayer. Biophys J 106(6):1371–1380.
  • Sharp KA, Kasinath V, Wand AJ (2014) Banding of NMR-derived methyl order parameters: Implications for protein dynamics. Proteins, in press.
  • Villali J, Pontiggia F, Clarkson MW, Hagan MF, Kern D (2014) Evidence against the "Y-T coupling" mechanism of activation in the response regulator NtrC. J Mol Biol 426(7):1554–1567.
  • Weingarth M, van der Cruijsen EA, Ostmeyer J, Lievestro S, Roux B, Baldus M (2014) Quantitative analysis of the water occupancy around the selectivity filter of a K+ channel in different gating modes. J Am Chem Soc. 136(5):2000–2007.

2013

  • Andersson M, Ulmschneider JP, Ulmschneider MB, White SH (2013) Conformational states of melittin at a bilayer interface. Biophys J 104(6):L12–L14.
  • Bastidas M, Showalter SA (2013) Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters. J Mol Biol 425(18):3360–3377.
  • Bjelic S, Nivon L, Çelebi-Ölçüm N, Kiss G, Rosewall C, Lovick H, Ingalls E, Gallaher J, Seetharaman J, Lew S, Montelione G, Hunt J, Michael F, Houk KN, Baker D (2013) Computational design of enone-binding proteins with catalytic activity for the Morita–Baylis–Hillman Reaction. ACS Chem Biol, 8(4):749–757.
  • Farelli JD, Gumbart JC, Akey IV, Hempstead A, Amyot W, Head JF, McKnight CJ, Isberg RR, Akey CW (2013) IcmQ in the Type 4b secretion system contains an NAD+ binding domain. Structure 21(8):1361–1373.
  • Geng R, Sotomayor M, Kinder KJ, Gopal SR, Gerka-Stuyt J, Chen DH, Hardisty-Hughes RE, Ball G, Parker A, Gaudet R, Furness D, Brown SD, Corey DP, Alagramam KN (2013) Noddy, a mouse harboring a missense mutation in protocadherin-15, reveals the impact of disrupting a critical interaction site between tip-link cadherins in inner ear hair cells. J Neurosci 33(10):4395–4404.
  • Gumbart JC, Roux B, Chipot C (2013) Efficient determination of protein–protein standard binding free energies from first principles, J Am Chem Soc, 9(8): 3789–3798.
  • Gumbart JC, Teo I, Roux B, Schulten K (2013) Reconciling the roles of kinetic and thermodynamic factors in membrane–protein insertion. J Am Chem Soc 135(6):2291–2297.
  • Gur M, Zomot E, Bahar I (2013) Global motions exhibited by proteins in micro- to milliseconds simulations concur with anisotropic network model predictions. J Chem Phys 139(12):121912.
  • Huang W, Kim J, Jha S, Aboul-ela F (2013) The impact of a ligand binding on strand migration in the SAM-I riboswitch. PLoS Comput Biol. 9(5):e1003069.
  • Kasinath V, Sharp KA, Wand AJ (2013) Microscopic insights into the NMR relaxation based protein conformational entropy meter. J Am Chem Soc, 135(4):15092–15100.
  • Kunze MBA, Wright DW, Werbeck ND, Kirkpatrick J, Coveney PV, Hansen DF (2013) Loop interactions and dynamics tune the enzymatic activity of the human histone deacetylase 8. J Am Chem Soc, in press
  • Kurnikov IV, Kyrychenko A, Flores-Canales JC, Rodnin MV, Simakov N, Vargas-Uribe M, Posokhov YO, Kurnikova M, Ladokhin AS (2013) pH-triggered conformational switching of the diphtheria toxin T-domain: the roles of N-terminal histidines. J Mol Biol 425(15):2752–2764.
  • Kwon T, Dowd TL, Bargiello TA (2013) The carboxyl terminal residues 220-283 are not required for voltage gating of a chimeric connexin32 hemichannel. Biophys J 105(6):1376–1382.
  • Kwon T, Tang Q, Bargiello TA (2013) Voltage-dependent gating of the Cx32*43E1 hemichannel: Conformational changes at the channel entrances. J Gen Physiol 141(2):243–259.
  • Li J, Enkavi G, Wen P-C, Shaikh SA, Tajkhorshid E (2013) Transient formation of water-conducting states in membrane transporters. Proc Nat Acad Sci USA 110(19):7696–7701.
  • Liang G, Zhao J, Yu X, Zheng J (2014) Comparative molecular dynamics study of human islet amyloid polypeptide (IAPP) and rat IAPP oligomers. Biochemistry 52(6):1089–1100.
  • McNulty R, Ulmschneider JP, Luecke H, Ulmschneider MB (2013) Mechanisms of molecular transport through the urea channel of Helicobacter pylori. Nature Commun. 2900:1–10.
  • Noel JK, Onuchic, JN, Sulkowska JI (2013) Knotting a protein in explicit solvent. J Phys Chem Lett 4(21):3570–3573.
  • Noinaj N, Kuszak AJ, Gumbart JC, Lukacik P, Chang H, Easley NC, Lithgow T, Buchanan SK (2013) Structural insight into the biogenesis of β-barrel membrane proteins. Nature 501(7467):385–390.
  • Ortega DR, Yang C, Ames P, Baudry J, Parkinson JS, Zhulin IB (2013) A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors. Nat Commun. 2881:1–8.
  • Ostmeyer J, Chakrapani S, Pan AC, Perozo E, Roux B (2013) Recovery from slow inactivation in K+ channels is controlled by water molecules. Nature 501(7465):121–124.
  • Prigozhin MB, Liu Y, Wirth AJ, Kapoor S, Winter R, Schulten K, Gruebele M (2013) Misplaced helix slows down ultrafast pressure-jump protein folding. Proc Natl Acad Sci USA 110(20):8087–8092.
  • Salmon L, Bascom G, Andricioaei I, Al-Hashimi HM (2013) A general method for constructing atomic-resolution RNA ensembles using NMR residual dipolar couplings: The basis for interhelical motions revealed. J Am Chem Soc, 135(14):5457–5466.
  • Shaikh SA, Li J, Enkavi G, Wen P-C, Huang Z, Tajkhorshid E (2013) Visualizing functional motions of membrane transporters with molecular dynamics simulations. Biochemistry 52(4):569–587.
  • Sharp K (2013) Calculation of molecular entropies using temperature Integration. J Chem Theor Comput, 9(2):1164–1172.
  • Sodt AJ, Sandar ML, Gawrisch K, Pastor RW, Lyman E (2013) The molecular structure of the liquid-ordered phase of lipid bilayers. J Am Chem Soc 136(2):725–732.
  • Ulmschneider MB, Bagnéris C, McCusker EC, Decaen PG, Delling M, Clapham DE, Ulmschneider JP, Wallace BA (2013) Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel. Proc Natl Acad Sci USA. 110(16):6364–6369.
  • Wei C, Pohorille A (2013) Activation and proton transport mechanism in influenza A M2 channel. Biophys J, 105(9):2036–2045.
  • Zhang L, Buck M (2013) Molecular simulations of a dynamic protein complex: role of salt-bridges and polar interactions in configurational transitions. Biophys J 105(10):2412–2417.
  • Zomot E, Bahar I (2013) Intracellular gating in an inward-facing state of aspartate transporter GltPh is regulated by the movements of the helical hairpin HP2. J Biol Chem 288(12):8231–8237.

2012

    • Bhattacharya S, Derrington IM, Pavlenok M, Niederweis M, Gundlach JH, Aksimentiev A (2012) Molecular dynamics study of MspA arginine mutants predicts slow DNA translocations and ion current blockades indicative of DNA sequence. ACS Nano 6(8):6960–6968.
    • Freites JA, Schow EV, White SH, Tobias DJ (2012) Microscopic origin of gating current fluctuations in a potassium channel voltage sensor. Biophys J 102(11):L44–L46.
    • Lindert S, Kekenes-Huskey PM, McCammon JA (2012) Long-timescale molecular dynamics simulations elucidate the dynamics and kinetics of exposure of the hydrophobic patch in troponin C. Biophys J 103(8):1784–1789.
    • Liu Y, Strümpfer J, Freddolino PL, Gruebele M, Schulten K (2012) Structural characterization of λ-repressor folding from all-atom molecular dynamics simulations. J Phys Chem Lett 3(9):1117–1123.
    • Maffeo C, Bhattacharya S, Yoo J, Wells D, Aksimentiev A (2012) Modeling and simulation of ion channels. Chem Rev 112(12):6250–6284.
    • Razavian NS, Kamisetty H, Langmead CJ (2012) Learning generative models of molecular dynamics. BMC Genomics 13(Suppl 1):S5.
    • Rogaski B, Klauda JB (2012) Membrane-binding mechanism of a peripheral membrane protein through microsecond molecular dynamics simulations. J Mol Biol 423(5)847–886.
    • Sotomayor M, Weihofen WA, Gaudet R, Corey DP (2012) Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Nature 492(7427):128–132.
    • Wan S, Wright DW, Coveney PV (2012) Mechanism of drug efficacy within the EGF receptor revealed by microsecond molecular dynamics simulation. Mol Cancer Ther 11(11):2394–2400.
    • Wright DW, Wan S, Shublaq N, Zasada SJ, Coveney PV (2012) From base pair to bedside: molecular simulation and the translation of genomics to personalised medicine. Wiley Interdiscip Rev Syst Biol Med 4(6):585–589.
    • Yu X, Wang Q, Lin Y, Zhao J, Zhao C, Zheng J (2012) Structure, orientation, and surface interaction of Alzheimer amyloid-β peptides on the graphite. Langmuir 28:6595–6605.
    • Zhang B, Miller TF 3rd. (2012) Direct simulation of early-stage Sec-facilitated protein translocation. J Am Chem Soc 134(33):13700–1370.
    • Zhang B, Miller TF 3rd. (2012) Long-timescale dynamics and the regulation of Sec-facilitated protein translocation. Cell Rep 2(4):927–937.
    • Zhao J, Luo Y, Jang H, Yu X, Wei G, Nussinov R, Zheng J (2012) Probing ion channel activity of human islet amyloid polypeptide (amylin). Biochim Biophys Acta 1818(12):3121–3130.

2010

  • Ramanathan A, Agarwal PK, Kurnikova M, Langmead CJ (2010) An online approach for mining collective behaviors from molecular dynamics simulations. J Comput Biol 17(3):309–324.

 

 

 

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