Anton 3

Logo consisting of Anton name

Anton is a special-purpose supercomputer for biomolecular simulation designed and constructed by D. E. Shaw Research (DESRES).  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.

PSC’s current system, Anton 2, is a second-generation Anton machine. It will remain operational until November 30, 2024. Information on Anton 2 can be found on the Anton 2 page.

Anton systems were designed to vastly accelerate the process of molecular dynamics (MD) simulation. With Anton, biomedical researchers can gain valuable insight into the motions and interactions of proteins and other biologically important molecules. The MD research community uses Anton at PSC to investigate significant biological phenomena that due in part to their intrinsically long timescales have been outside the reach of even the most powerful general-purpose supercomputers.

The third-generation Anton is the first and only resource available to the community capable of simulating multiple millions of atoms at speeds of microseconds per day, thus achieving biologically relevant timescales in a timely manner. The ability to simulate millions of atoms in a reasonable timeframe will bring new understanding of large biological systems such as viruses and ribosomes and of phenomena that occur in the millisecond timescale, such as protein folding, aggregation, and membrane deformations.

Anton at PSC is 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 operational support from the NIH National Institute of General Medical Sciences.

Apply

Anton is allocated annually via a Request for Proposals with proposals reviewed by a committee convened by the National Research Council at the National Academies of Sciences, Engineering, and Medicine.

To qualify for an allocation on Anton, the principal investigator must be a faculty or staff member at a US academic or not-for-profit research institution.

The Anton RFP period is closed. Be sure to watch for an announcement about the next RFP opportunity next summer.

 

Preparing a proposal

To help with proposal submissions, we presented two webinars on September 23, 2024:

2:00-3:00 PM (EDT)   – Anton 3 Capabilities and Enhanced Sampling Techniques 

This webinar introduced the third-generation Anton system to the research community, explaining its capabilities and enhanced sampling techniques.

3:00-4:00 PM (EDT)  – How to Write a Successful Anton Proposal 

This webinar explained how to prepare a successful application and who qualifies to apply.

Update:  The minimum number of atoms has been lowered to 100,000.

Using Anton 3

Documentation on using Anton 3 will be available by early 2025.

Instructions to use Anton 2 can be found on the Anton 2 page.

Anton End User Agreement

Please review the terms and conditions of the End User Agreement (EUA) for the Use of Anton at PSC before submitting a proposal.

Once the awards have been made, a form will be provided through which you can acknowledge that you have read, understood, and agreed to your responsibilities as an Anton user by accepting the terms and conditions of the Anton 3 EUA.

 All users, including PIs and group members, who are awarded time on Anton 3 must agree to the terms of the EUA before they receive access to Anton or to the introductory workshop.

Introductory workshop

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

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 3

Anton 3 computer time was provided by the Pittsburgh Supercomputing Center (PSC) through Grant 1R24GM154042 from the National Institutes of Health. The Anton 3 machine at PSC is made available by D. E. Shaw Research.

The proper citation for Anton 3 is:

Shaw DE, Adams PJ, Azaria A, Bank JA, Batson B, Bell A, et al. Anton 3: twenty microseconds of molecular dynamics simulation before lunch. SC ’21: The International Conference for High Performance Computing, Networking, Storage and Analysis. ACM; 2021. https://doi.org/10.1145/3458817.3487397

 

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 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 made available by D.E. Shaw Research.

The proper citation for Anton 1 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).

Anton in action

Learn about some of the groundbreaking research Anton at PSC has enabled over the years.

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.

Publications

View publications enabled by research that made use of Anton systems at PSC.

Research highlights

Here are a few highlights of the research enabled by Anton systems 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 3 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.