Introduction

The National Resource for Biomedical Supercomputing (NRBSC) is soliciting proposals for computer time on Anton, a special-purpose supercomputer for molecular dynamics (MD) simulation designed by D. E. Shaw Research (DESRES). A 512-node Anton machine is currently available and in production use at NRBSC at the Pittsburgh Supercomputing Center (PSC). The machine has been made available without cost by DESRES for non-commercial research use by universities and other not-for-profit institutions and is hosted by NRBSC with funding from the National Institute of General Medical Sciences under grant RC2GM093307. This RFP solicits proposals for an extension period beyond the originally planned project duration.

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 and must have the appropriate level of authority and responsibility to direct the project supported by the allocation. A graduate student or postdoctoral researcher may not be a PI, but a qualified advisor may apply for an allocation on her or his behalf. Furthermore, each investigator can serve as a PI for only a single application for computer time on Anton. Investigators who previously had an allocation on Anton at NRBSC are encouraged to apply but are required to provide a detailed (2-3 page) progress report of their past work on the Anton machine at NRBSC. Repeat applicants’ proposals should strongly argue why — based on past progress — additional time should be awarded. Repeat applications unaccompanied by a progress report will not be considered.

The remainder of this Request for Proposals (RFP) describes the intended focus of solicited projects, outlines simulation requirements, offers proposal preparation instructions, and explains the proposal review process.

Intended Focus of Proposed Projects

Anton enables scientists to perform MD simulations of biomolecular systems nearly two orders of magnitude faster than the previous state of the art (see the Estimating Requested Simulation Resources section). To maximize the benefit of Anton to the scientific community, proposed projects should focus exclusively on questions that will be greatly advanced by multi-microsecond MD simulations. Special emphasis should be on the need for long continuous trajectories rather than a sampling of many short ones. Further, investigators should explain why such long timescales are necessary and important for the molecular system and scientific question under consideration. Proposals to run only a large number of shorter simulations will receive a lower ranking in the review process.

Simulation Requirements

Anton uses specialized hardware to perform molecular dynamics simulations orders of magnitude faster than general purpose hardware running traditional MD software (see References 1 and 2 below). Importantly, Anton does not run Desmond, AMBER, NAMD, GROMACS, or any other MD simulation software package, although it uses a Desmond structure (Maestro or DMS) file as an initial input and its trajectory output is compatible with Desmond’s (DTR files). Each simulation must be built, using tools available at NRBSC, specifically for Anton.

Anton is designed primarily to accelerate classical MD simulations of biomolecular systems with periodic boundary conditions and explicit solvent. To make best use of the available computational resources, consideration will be given only to applicants whose projects satisfy the criteria outlined below. Investigators who have questions regarding the suitability of their proposed simulations are encouraged to contact to discuss their planned project before submitting their proposal.

1. Proposed simulations must be standard MD runs in the NVE, NVT (isothermal), and NPT (isothermal, isobaric) ensembles. 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, (ii) application of restraints between the centers of mass of (small) groups of atoms, and (iii) application of a conformational restraint based on the calculation of RMSD (root mean squared deviation) to atomic positions of a reference structure(s).
2. The simulation cell must have only right angles (i.e., a cubic or orthorhombic box). Applicants with systems shaped such that one dimension of the simulation cell is much larger than the others should contact before submitting a proposal.
3. Proposed simulations must 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 should be modeled with the SPC, TIP3P, or TIP4P models, or their variants.
4. Chemical systems proposed for simulation must contain between 20,000 and 120,000 atoms (including solvent atoms). Chemical systems proposed for simulation must consist of some combination of protein, DNA, RNA, lipids, water, and standard ions. Investigators who wish to use custom parameters or molecules that are not included in the standard distribution of the supported force fields (see 3 above) should contact to discuss the suitability of their simulations before submitting their proposal.

Estimating Requested Simulation Resources

Applicants may refer to the table below, with benchmarks for a number of systems of various sizes, to estimate the amount of machine time required for their project. The actual achievable simulation times, however, may vary even for different molecular systems of similar size. No more than a total of 8.14 machine-days (100,000 node-hours) will be allocated to any one principal investigator. It is anticipated that 10 to 15 allocations will be made at or near 100,000 node-hours, and 20 to 30 allocations will be made at or near 50,000 node-hours. Applicants are encouraged to target their requested resources at one of these levels. Note that simulations on Anton will run on all 512 nodes.

For more details regarding Anton, please see the References.

*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. Performance was measured on a 512-node Anton machine like the one hosted by the NRBSC.

Structure of Proposal

Proposals should be two to six pages in length, not including references. Investigators who previously received an allocation on Anton at NRBSC must also provide a separate 2-3 page progress report demonstrating their successful use of Anton to produce high-impact scientific results. In addition, applicants may submit up to two additional supporting documents (e.g., published papers) in PDF format on the submission page. The main proposal document must have the following sections:

1. Summary of the project, including descriptive title of proposed research (400 words maximum).
2. Name, address, email, and telephone number of Principal Investigator(s).
3. Background information (1 page maximum). Investigators should include sufficient background information on the research field to allow reviewers to judge the scientific merit of the proposed research.
4. Scientific Objectives to be accomplished on Anton (2 pages maximum). Investigators should clearly explain why long-timescale MD simulations are important for the planned project (see the Intended Focus of Proposed Projects section for more details). Applicants should also clearly explain the scientific impact of their proposed project.
5. Project Feasibility (2 page maximum). Applicants must clearly and explicitly address all four points outlined in the Simulation Requirements section of this RFP, providing all necessary details regarding their proposed simulations and the expertise of their research team members (including prior experience running MD simulations) to ensure that the proposed simulations can be successfully completed on Anton.
6. Requested Resources (1 page maximum). Investigators must clearly state and provide justification for the number of Anton node-hours requested for their project. The number of node-hours is 512 times 24 times the number of machine-days. The justification should provide strong scientific arguments as to why the length and number of proposed simulation runs will be both sufficient and necessary to achieve the stated scientific objectives. Please refer to the Estimating Requested Simulation Resources section for benchmarks to facilitate estimation of requested resources.

Important Dates and Proposal Review Process

Proposals will initially be assessed for technical feasibility by NRBSC and PSC staff (see the Simulation Requirements section) and will then be reviewed by a peer committee to be convened by the National Research Council. Resource allocations will be made by NRBSC following the recommendations of the National Research Council. Final allocation decisions are expected in late August 2011. Resources are expected to be made available starting in late 2011.

Proposals will be ranked based on the scientific merit of the proposed research and the strength of the justification for the requested resources. In addition, proposals by PIs that previously received an allocation on Anton at NRBSC will need to demonstrate that the scientific outcomes from the first award justify a second award. At least half of the total allocated time will be reserved for PIs that have not previously had an allocation on Anton at NRBSC. Since only a limited number of allocations will be available on Anton, a successful proposal will clearly state how access to Anton will facilitate breakthrough science.

For general questions regarding this RFP, or to discuss feasibility and technical aspects of projects, please contact .

References

[1] Millisecond-Scale Molecular Dynamics Simulations on Anton, D. E. Shaw et al., Proceedings of the ACM/IEEE Conference on Supercomputing (SC09), Portland, Oregon (2009)
[2] Anton, A Special-Purpose Machine for Molecular Dynamics Simulation, D. E. Shaw et al., Proceedings of the 34th Annual International Symposium on Computer Architecture (ISCA ‘07), (2007)
[3] http://www.deshawresearch.com/publications.html