Anton 2

Anton is a special purpose supercomputer for biomolecular simulation designed and constructed by D. E. Shaw Research (DESRES). PSC’s current system is known as Anton 2 and is a successor to the original Anton machine hosted here.

Anton 2, the second-generation Anton supercomputer, is a 128 node system, made available without cost by DESRES for non-commercial research use by US universities and other not-for-profit institutions, and is hosted by PSC with support from the NIH National Institute of General Medical Sciences. It replaced the original Anton system in the Fall of 2016.

Anton systems were designed to dramatically increase the speed of molecular dynamics (MD) simulations compared to available state-of-the-art systems, allowing biomedical researchers to understand the motions and interactions of proteins and other biologically important molecules over much longer time periods than was previously accessible to computational study. The MD research community is using the Anton machine at PSC to investigate important biological phenomena that due to their intrinsically long time scales have been outside the reach of even the most powerful general-purpose scientific computers. Application areas include biomolecular energy transformation, ion channel selectivity and gating, drug interactions with proteins and nucleic acids, protein folding and protein-membrane signaling.

Anton 2 will remain operational until November 30, 2024. PSC eagerly anticipates that the third-generation Anton system, Anton 3, will become operational at PSC in early spring 2025. See the Anton 3 page for more information.

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Using Anton 2

PIs and group members must submit a signed End User Agreement before accounts for Anton or access to the Anton workshop can be granted.

Documentation

Anton 2 documentation and instructions are found on the Anton Wiki. This wiki can be accessed with your PSC username/password credentials. If you forget your password, you can reset it using the following link: apr.psc.edu.

Introductory workshop

A workshop covering all aspects of running MD simulations on Anton is presented each fall. It is offered by invitation only to the most recent allocations awardees.

View the agenda for the most recent workshop.

Support and community

The preferred way of communicating with PSC support staff and with other users who share their experiences is through the Anton forum on the wiki. Please sign up here: https://wiki.psc.edu/twiki/view/Anton/AntonForumSign

If you experience difficulties after registering, please check the Anton Forum section of the wiki to ensure your issue has not been addressed before. There is a text file to make it easier to search, and sections for frequently asked questions and troubleshooting tips. If your problem hasn’t been addressed already, please feel free to email anton-forum@psc.edu for help.

Anton End User Agreement

All users who are awarded time on Anton must agree to the terms of the End User Agreement (EUA) before they receive access to Anton.

You must complete and submit the End User Agreement for the Use of Anton at PSC form to acknowledge that you have read, understood, and agreed to your responsibilities as an Anton user.

View the EUA terms and conditions

Acknowledgement in publications

Please use the following paragraph (or similar) to cite your work conducted on Anton. Proper acknowledgment is critical for our ability to solicit continued funding for the project.

Acknowledgement for Anton 2

Anton 2 computer time was provided by the Pittsburgh Supercomputing Center (PSC) through Grant R01GM116961 from the National Institutes of Health. The Anton 2 machine at PSC was generously made available by D.E. Shaw Research.

The proper citation for Anton 2 is:

Shaw, David E., J.P. Grossman, Joseph A. Bank, Brannon Batson, J. Adam Butts, Jack C. Chao, Martin M. Deneroff, et al. “Anton 2: Raising the Bar for Performance and Programmability in a Special-Purpose Molecular Dynamics Supercomputer,” 41–53. IEEE, 2014. doi:10.1109/SC.2014.9.

Acknowledgement for Anton 1

Anton computer time was provided by the Pittsburgh Supercomputing Center (PSC) through Grant R01GM116961 from the National Institutes of Health. The Anton machine at PSC was generously made available by D.E. Shaw Research.

The proper citation for the Anton machine is:

Millisecond-Scale Molecular Dynamics Simulations on Anton, D. E. Shaw et al., Proceedings of the ACM/IEEE Conference on Supercomputing (SC09), Portland, Oregon (2009).

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Apply

Anton 2 will remain operational until November 30, 2024, but no additional allocations will be awarded on it.

PSC eagerly anticipates that the third-generation Anton system, Anton 3, will become operational at PSC in early spring 2025. This 64-node Anton system will replace and greatly enhance the capabilities of PSC’s current second-generation machine.

The Anton 3 Request for Proposals is now open. The deadline to apply is 11:59 PM Eastern time, Monday, October 14, 2024.

See the Anton 3 page for more information

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Anton in action

Learn about some of the groundbreaking research that the first- and second-generation Anton machines have enabled over the years.

Project summaries

Check back soon for a sampling of project summaries from Anton 1 research.

Publications

View publications enabled by research that made use of the first- and second-generation Anton sytems at PSC.

Anton Simulations Reveal How Alzheimer’s Fibril Growth May Accelerate

Unexpected Way for Amyloid Peptides to Join Fibrils Explains Time Lag, then Accelerated Growth, in Fibril Formation and Disease Progression

$3.15 Million from NIH to Fund Operation of Third-Generation Anton Supercomputer at Pittsburgh Supercomputing Center

Designed and Built by D. E. Shaw Research, System Will Simulate Biomolecules Roughly 100 Times Faster than General-Purpose Supercomputers

Anton Simulations Explain Delay in CRISPR-Cas12a’s DNA-Cutting Function

Understanding Unexpected Motion of Protein Will Be Crucial for Engineering it for DNA Detection, Editing

Voltage-sensing Protein Moves in Unexpected Ways in Anton Simulations

University of Chicago Simulations Offer Clues to Behavior of Nerve Cell Channels Underlying Human Diseases

“Invisible” Protein Movements Revealed by Anton 2 Simulations

Interactions not before seen between medically important beta-adrenergic receptor and its associated G protein offer clues to better heart, lung, and other medications.

Anton 2 Simulations Reveal Unexpected Role for Brain Neurotransmitter

Ability of D-serine to switch from boosting excitatory signals to blocking them suggests route for preventing long-term injury or stroke damage

Anton 2, Bridges-2 Simulations Explain Life-Critical Protein in the Brain

Complementary strengths of researchers, computers help identify structure and motions of protein and its electrical conductance through the nerve-cell membrane

Anton 2 Sims Suggest How Fish Oil Health Benefits Start at Cell Membrane

Molecular simulations coupled with AI analysis reveal how omega-3 polyunsaturated fatty acids may regulate the size of membrane “rafts”

Anton 2 Simulations Explain Mechanism for Loading DNA into Virus

Two-phase Motor Packages DNA into Viral Capsids, May Offer Drug Target

Anton 2 Operational

Anton 2, a specialized supercomputer developed by D. E. Shaw Research that simulates the motions of biomolecules, has replaced the original Anton 1 system previously at PSC. The new machine, operationally supported through a grant from the National Institutes of Health, enables life scientists to simulate much larger biomolecules for longer timescales than was previously feasible.

Research highlights

Here are a few highlights of the research enabled by the first- and second-generation Anton machines at PSC:

Protein dehydration during folding. The team combined 110 μs Anton 2 MD simulations with rapid pressure-drop experiments to study how water gets out of a protein as it folds. Prigozhin, Maxim B., Yi Zhang, Klaus Schulten, Martin Gruebele, and Taras V. Pogorelov PNAS, 2019. https://doi.org/10.1073/pnas.1814927116.

Molecular mechanisms of cataract formation – Identified the enhanced inter-protein interactions that lead to large-scale aggregation. Wong, Eric K., Vera Prytkova, J. Alfredo Freites, Carter T. Butts, and Douglas J. Tobias. Biochemistry 2019. https://doi.org/10.1021/acs.biochem.9b00208.

Molecular mechanisms of arrestin activation – Simulations provide a structural foundation for the design of functionally selective ligands that lead to particular GPCR signaling profiles. N. Latorraca and R. Dror. doi:10.1038/s41586-018-0077-3

Uncovering new ways to target flu viruses – A conserved amino acid could provide a target toward a universal vaccine for viruses. Xingcheng Lin, Jeffrey K. Noel, Qinghua Wang, Jianpeng Ma, and Jose Onuchic. doi:10.1073/pnas.1805442115.

Kink formation is required for lateral gating in BamA – Simulations of BamA reveal a dynamic gating between the N- and C-terminal strands at the barrel seam. Using free-energy calculations and mutagenesis experiments, it was determined that the C-terminus has to kink inward for efficient opening. lateral gating in BamA. Karl Lundquist, Jeremy Bakelar, Nicholas Noinaj, and JC Gumbart. doi:10.1073/pnas.1722530115

World’s Tiniest Test Tubes in Alzheimer’s Protein Simulation – Simulations of plaque-forming beta amyloid molecules offer insights towards possible Alzheimer’s drug therapies. From PSC’s Science Highlights Fall 2018. G. Eskici and P.H. Axelsen. doi:10.1021/acs.langmuir.7b04192.

“Sticky and Loose Ends” Shed Light on Heart Health – Simulations show APOA1 protein ends link to hold together “the good cholesterol”. From PSC’s Science Highlights Fall 2018. Mohsen Pourmousa, Richard Pastor, Jere Segrest, et. al. doi: 10.1073/pnas.1721181115

Locked, Not Loaded – New target in HIV-1 replication. Simulations may lead to more effective anti-maturation drugs to fight AIDS and possibly other viral diseases. From PSC’s Science Highlights Spring 2018. J. Perilla et al. doi:10.1038/s41467-017-01856-y.

Snapping into Place – Simulations give clue to poorly understood role of tubulin, the cell’s “Lego bricks”. From PSC’s Science Highlights Spring 2018. David Hoogerheide. doi:10.1073/pnas.1721181115.

Inner Space – Work on Anton highlights the importance of empty space for protein function. Simulations of T4 lysozyme L99A show that big gaps opened up in the protein, which “let in” molecules roughly the size of drug molecules. From PSC’s Science Highlights Fall 2017.

Hooked Up – Simulations on Anton discover the critical role disulfides play in holding together MCoTI-II, a natural pesticide that would fall apart without disulfide bridges. From PSC’s Science Highlights Spring 2017.

“The Dynamics of Single Protein Molecules Is Non-Equilibrium and Self-Similar over Thirteen Decades in Time.” Nature Physics 12, no. 2 (2016): 171–74. doi:10.1038/nphys3553. Hu, Xiaohu, Liang Hong, Micholas Dean Smith, Thomas Neusius, Xiaolin Cheng, and Jeremy C. Smith. This article was highlighted in the cover of Nature Physics and discussed in the following article: Metzler R, News and Views Protein physics: Forever ageing, Nature Phys., 2016, 12, 113–114, doi:10.1038/nphys3585.

“Disulfide Bridges: Bringing Together Frustrated Structure in a Bioactive Peptide”. Biophysical Journal 110, no. 8 (April 2016): 1744–52. doi:10.1016/j.bpj.2016.03.027. Zhang, Yi, Klaus Schulten, Martin Gruebele, Paramjit S. Bansal, David Wilson, and Norelle L. Daly. This article was featured on the cover of the Biophysical Journal.

“Hexagonal Substructure and Hydrogen Bonding in Liquid-Ordered Phases Containing Palmitoyl Sphingomyelin.” Biophysical Journal 109, no. 5 (September 2015): 948–55. doi:10.1016/j.bpj.2015.07.036 Sodt, Alexander J., Richard W. Pastor, and Edward Lyman. This study was featured on the cover of the Biophysical Journal and highlighted as New and Notable: http://www.cell.com/biophysj/abstract/S0006-3495(15)00772-9

Janus Channel – Anton simulations reveal how pain, epilepsy drugs work through same target protein, from PSC’s Projects in Scientific Computing, Spring 2015.

A TUG Felt Elsewhere – Anton simulations show how drug-producing enzyme is enhanced by changes far from reactive site, from PSC’s Projects in Scientific Computing, Fall 2014.

Roll Out the Beta Barrels – Anton simulations reveal how dangerous bacteria install critical proteins, from PSC’s Projects in Scientific Computing, Spring 2014.

Two Steps Forward, One Step Back – molecular dynamics simulations disclose how water leaving and then re-entering the potassium channel delays its return to the active state, from PSC’s Projects in Scientific Computing, Spring 2014.

A Movie is Worth a Million Pictures – structural dynamics simulations illuminate the mechanisms of sodium-coupled substrate binding/release in an aspartate transporter, from PSC’s 2013 annual report, Projects in Scientific Computing

Epic Microseconds – four projects yielding invaluable insights into the structure and function of proteins from PSC’s 2012 annual report, Projects in Scientific Computing

Protein Research Leaps Forward – four projects in MD simulation from PSC’s 2011 annual report, Projects in Scientific Computing

Atomic-Level Characterization of the Structural Dynamics of Proteins – This paper, published in Science, details the first millisecond MD simulation on Anton.
Shaw, David E., Paul Maragakis, Kresten Lindorff-Larsen, Stefano Piana, Ron O. Dror, Michael P. Eastwood, Joseph A. Bank, John M. Jumper, John K. Salmon, Yibing Shan, Willy Wriggers. “Atomic-Level Characterization of the Structural Dynamics of Proteins” Science 15 Oct 2010: 341-346 DOI: 10.1126/science.1187409

Millisecond-scale molecular dynamics simulations on Anton – This paper (Gordon Bell prize winner for best paper at SC09 ) contains measurements of energy conservation on Anton that you can use to compare with your own simulations.

The operations of Anton at PSC are supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number 1R24GM154042. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.