Summary

This document describes the work and transmits the decisions of the Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics, Sixteenth Round.

The committee evaluated submissions received in response to a request for proposals (RFP) for Biomolecular Simulation Time on Anton 3, a supercomputer designed and built by D. E. Shaw Research (DESRES). Over the past 15 years, DESRES has made an Anton system housed at the Pittsburgh Supercomputing Center (PSC) available to the non-commercial research community, based on the advice of previous committees of the National Academies of Sciences, Engineering, and Medicine (the National Academies). In 2025, Anton 2 was replaced by a 64-node third-generation Anton machine, Anton 3. This new machine greatly enhances the capabilities of the previous generation of Anton systems. As in prior rounds, the goal of the sixteenth RFP for simulation time on Anton 3 is to continue to facilitate breakthrough research in the study of biomolecular systems by providing a massively parallel system specially designed for molecular dynamics (MD) simulations. These capabilities allow for multi-µs simulation timescales. The program seeks to continue to support research that addresses important and high impact questions demonstrating a clear need for Anton’s special capabilities.

The success of the program has led DESRES to make the Anton 3 machine housed at PSC available for approximately 330 machine days (MDs) over the period following April 2026, and DESRES asked the National Academies to again facilitate the allocation of time to the noncommercial community. The work of the committee to evaluate proposals for time allocations was supported by a contract between DESRES and the National Academy of Sciences and was performed under the auspices of the National Academies’ Life Sciences and Biotechnology Program Area.

To undertake this task, the National Academies convened a selection committee of experts to evaluate the proposals submitted in response to the RFP. The committee of 21 was chaired by Dr. Wong Chung, a Professor of Chemistry and Biochemistry at the University of Missouri–St. Louis. The committee members were selected for their expertise in MD simulations and experience in the subject areas represented in the 60 proposals that were considered. The members comprised a cross-section of the biomolecular dynamics field in academia, including both senior and junior investigators.

The Anton 3 RFP described the three criteria against which the committee was asked to evaluate proposals:

• Level of Scientific Merit, including the potential to advance understanding on an important problem or question in the field; the potential for breakthrough science resulting in new discoveries and understanding; the impact that successful completion of the proposed research would have on knowledge, methods, and current barriers in the field; and a scientifically and technologically feasible project with clear, well-developed, and appropriate goals, objectives, and approaches to the proposed studies.
• Justification for Requested Time Allocation, including a clear and convincing justification that the length and number of proposed simulation runs and node-hours requested are necessary and sufficient to achieve the scientific objectives.

• Investigator Qualifications and Past Accomplishments, including the appropriate experience and training to successfully conduct the proposed studies, evidence of knowledge and prior experience in molecular simulations, and past publications.

Proposals from investigators who had previously received an allocation of time on Anton or Anton 2 were required to include progress reports, which the committee drew on as supplemental material in its consideration of proposals. As explained in the RFP, staff at PSC conducted an initial assessment of all proposal submissions for completeness and to determine if they were technically feasible for simulation on Anton 3. Two members of the PSC staff were present as observers during committee discussions to address any additional questions that arose regarding the technical capabilities of Anton 3 or on how the computer will be made available to researchers during the period of the project.

The committee was asked to identify proposals that best met the selection criteria defined above. The maximum time allocation available per proposal was 9.1 MDs. Principal investigators (PIs) could also request a smaller time allocation. The committee was permitted, at its discretion, to consider a modified time allocation than otherwise requested. The committee was further asked to target, to the extent possible, at least 25 percent of allotted time to PIs who had not previously received an Anton allocation. The judgments of the committee are based on which proposals best met the selection criteria described above and on the estimates of required simulation time provided by the applicants.

Initial reviews of the proposals were provided by the 21 committee members. Each proposal was assigned a minimum of two primary reviewers who were asked to evaluate the proposal based on the RFP and the guidelines described above. Review assignments were made so that proposals were not evaluated by reviewers from the applicant’s same institution or who had close collaborative or personal relationships with an applicant. These conflicts of interest (COIs) are included in Appendix G.

The committee held one virtual meeting and one hybrid proposal review meeting on December 8^th and 12^th, 2025, respectively. For the hybrid meeting, some committee members attended in person in Washington, DC while others joined virtually. At the meeting, the two primary reviewers were asked to summarize their reviews for the committee, which was followed by discussion of the proposed research. Committee members determined to have a COI with a proposal were excused from the committee discussion on that proposal and placed in a virtual waiting room (if virtual) or left the room (if in person) until discussion of the proposal was complete. As described in detail above, committee members considered the scientific merit, justification of the requested time, and the qualifications of the PI and key personnel. The committee reviewed the slate of proposals under consideration and selected proposals it judged best met the selection criteria, and, in some cases, decided to suggest a modified allocation of time on Anton 3. Detailed comments for each of the 60 proposals are included in Appendix B.

The committee judged that the proposals listed below best met the selection criteria set forth in the RFP for biomolecular simulation time on Anton 3. Of these 60 proposals, 26 proposals were selected for a modified allocation (identified below with an asterisk). The proposals judged by the committee as best meeting the selection criteria of the RFP are presented below in alphabetical and numerical order by proposal submission number:

BIO110002P Michael Grabe, University of California, San Francisco; Lipid sorting and scrambling by TMEM16F in complex asymmetric membranes [Returning user identified for 9 MDs]

CHE120043P Gregory A. Voth, University of Chicago; Mechanistic insights into viral infectivity and maturation in HIV-1 and SARS-CoV-2 [Returning user identified for 9 MDs]

CHE180044P Vincent Voelz, Temple University; Understanding multi-domain allostery through the conformational dynamics of human Pin1 [Returning user identified for 4.5 MDs]

IBN130013P Maria Bykhovskaia, Wayne State University; Protein Machinery Regulating Synaptic Vesicle Fusion [Returning user identified for 8.25 MDs]

IBN250000P Stefano Berto, Medical University of South Carolina; Modeling and Elucidation of CHAMP1-HP1α Binding Interactions [New user identified for 2 MDs]*

MCB100016P Aleksei Aksimentiev, University of Illinois at Urbana-Champaign; Nanopore Protein Sequencing with MspA [Returning user identified for 4.5 MDs]*

MCB100017P Emad Tajkhorshid, University of Illinois at Urbana-Champaign; Binding of Novel Antibiotics to the Multidrug Efflux Protein AcrB [Returning user identified for 7.2 MDs]

MCB110005P Douglas James Tobias, University of California, Irvine; Atomistic modeling of the pharmacological inhibition of the Hv1 proton channel [Returning user identified for 6 MDs]*

MCB110012P Jeffery B. Klauda, University of Maryland at College Park; Gating Mechanisms in HCN1 Channels: Molecular Dynamics Simulations of cAMP- and Voltage-Dependent Conformational Changes [Returning user identified for 9.1 MDs]

MCB110023P Matthias Buck, Case Western Reserve University; Computer Simulation of the Association of Full-length EphA2 RTK at the Membrane [Returning user identified for 4.58 MDs]

MCB110024P Marta Filizola, Icahn School of Medicine at Mount Sinai; Investigating the Molecular Basis of Ligand Efficacy in GPCR-Mediated G Protein Signaling [Returning user identified for 9.1 MDs]

MCB110059P Wonpil Im, Lehigh University; Induced Ordered Domains and Anesthetic Action in Asymmetric Bilayers [Returning user identified for 9.1 MDs]

MCB110066P Edward Lyman, University of Delaware; Asymmetric membrane model for a “typical” mammalian cell [Returning user identified for 4.5 MDs]*

MCB130048P David Cowburn, Albert Einstein College of Medicine; Simulation of the Nuclear Pore Core and Transport [Returning user identified for 7 MDs]*

MCB130052P Themis Lazaridis, The City University of New York; Modeling cytolytic membrane pores [Returning user identified for 3 MDs]*

MCB140052P Richard W. Pastor, National Institutes of Health; Mechanism of Cell Penetrating Peptides [Returning user identified for 9 MDs]

MCB150024P Marcos Sotomayor, University of Chicago; Predicting Membrane Deformation and Lipid Scrambling by Mechanosensitive Ion Channels [Returning user identified for 6 MDs]*

MCB160079P Sharon Loverde, The City University of New York; Molecular Dynamics Simulations of Chromatin Remodelers Bound to the Nucleosome [Returning user identified for 2.1 MDs]*

MCB160087P Mahmoud Moradi, University of Arkansas at Little Rock; Elucidating the Conformational Dynamics of Bacterial Collagenase colH Protein [Returning user identified for 3 MDs]*

MCB160089P Igor Vorobyov, University of California, Davis; Multi-microsecond-long molecular dynamics simulations to assess cardiac ion channel-drug interactions in complex cellular environments [Returning user identified for 7 MDs]*

MCB170088P Maria Kurnikova, Carnegie Mellon University; Structure, gating and ion permeation in glutamate receptor complexes with auxiliary proteins [Returning user identified for 4.5 MDs]*

MCB170100P Janice Robertson, Washington University in St. Louis; The effect of lipid chain entropy on protein association stability in membranes [Returning user identified for 9.1 MDs]

MCB180084P Juan Perilla, University of Delaware; Characterizing the role of the HIV-1 matrix (MA) protein in lipid ordering during viral maturation. [Returning user identified for 9.1 MDs]

MCB180091P William Goddard, California Institute of Technology; Molecular Mechanisms of Extra-Oral Bitter Taste Receptor Activation and Inhibition [Returning user identified for 4.5 MDs]*

MCB190044P Yun Luo, Western University of Health Sciences; Selective modulation of PIEZO1 channels by Yoda2 [Returning user identified for 3 MDs]*

MCB190070P Alexey Ladokhin, University of Kansas, All Campuses; Atomistic modeling of cancer-targeting peptide pHLIP P20G mutant on membrane interfaces [Returning user identified for 6 MDs]*

MCB200062P Qiang Cui, Boston University; Molecular Dynamics Simulation of Condensate/Membrane interaction in the FEME pathway [Returning user identified for 4.4 MDs]*

MCB200085P Jing Li, University of Mississippi, All Campuses; Elucidate Long-Range Allosteric Roles of Disease-Associated Mutations in hERG Inactivation and Deactivation [Returning user identified for 9.1 MDs]

MCB200087P Paul Robustelli, Dartmouth College; Molecular mechanisms of small molecules that modulate biomolecular condensates [Returning user identified for 9.1 MDs]

MCB200095P Taras Pogorelov, University of Illinois at Urbana-Champaign; Mechanistic Role of Dimeric Ensembles in Receptor Tyrosine Kinases [Returning user identified for 9.1 MDs]

MCB210005P Giulia Palermo, University of California, Riverside; Mechanistic Dissection of CRISPR-Associated Transposons (CASTs) via Anton 3 Simulations and AI-driven Approaches [Returning user identified for 7 MDs]*

MCB210016P Jessica Swanson, The University of Utah; Unraveling the Reductants and Lipid Impacts in Biological Methane Mitigation [Returning user identified for 6.05 MDs]

MCB210021P Sandhya Kortagere, Drexel University; Evaluating the dynamic interactions between PfATPase4 and its associated binding protein [Returning user identified for 1.87 MDs]

MCB220012P Irina Kufareva, University of California, San Diego; Dynamic Mechanisms and Consequences of the Noncanonical β-Arrestin Engagement by the Atypical Chemokine Receptor ACKR3 [Returning user identified for 4.1 MDs]

MCB240001P Carter Butts, University of California, Irvine; Effect of Oxidative Damage on Aggregation in the gammaS-crystallin Hydrogel [Returning user identified for 7.09 MDs]

MCB240005P Anna Tarakanova, University of Connecticut, All Campuses; Investigating the effects of missense mutations in elastin with molecular dynamics [Returning user identified for 9.1 MDs]

MCB240009P Yanxin Liu, University of Maryland, College Park; Molecular mechanism of client protein remodeling by the Hsp90 molecular chaperone [Returning user identified for 9.1 MDs]

MCB240011P Steve Cannon, University of California, Los Angeles; Simulated deactivation of the NaV1.4 sodium channel to define the proton leak through the voltage-sensor domain of a mutant channel causing periodic paralysis [Returning user identified for 9 MDs]

MCB240017P Premila Samuel Mohan Dass, Saint Louis University; Folding, mis-assembly, and aggregation pathways of human hemoglobin in red blood cell cytoplasm models [Returning user identified for 5 MDs]

MCB240020P Andrew Harris, Rutgers University; Dynamics, Structural and Energetic Basis of Connexin Hemichannel Docking and Regulation by Ca2+ [Returning user identified for 3 MDs]*

MCB250000P Yaxin An, Louisiana State University, All Campuses; Membranized biocondensates for drug delivery [New user identified for 4.5 MDs]

MCB250001P George Khelashvili, Weill Cornell Medical College; Mechanisms of STRA6mediated retinol transport [New user identified for 7 MDs]*

MCB250002P Yanxiao Han, University of North Texas; Unraveling ligand-induced biased signaling in βAR and GPER through long-timescale molecular dynamics simulations [New user identified for 4.5 MDs]*

MCB250005P Vardhan Satalkar, Molecular Biology Institute; Molecular Dynamics of IP3R Gating and ER-PM Junctional Regulation [New user identified for 4.5 MDs]

MCB250006P Milo Lin, UT Southwestern Medical Center; Simulating Amyloid Fibril Nucleation via xHAT Mechanism [New user identified for 4.5 MDs]*

MCB250007P Alina Emelianova, Princeton University; From Atomistic Validation to Coarse-Grained Discovery: MAPPS Framework for Biomolecular Condensate Modulation [New user identified for 6 MDs]*

MCB250008P Heather True, Washington University in St. Louis; All-Atom Investigation of Mutation-Dependent Secondary-Structure and Binding Dynamics in the Yeast Hsp40 Co-Chaperone Sis1 [New user identified for 4.5 MDs]*

MCB250009P Sapna Sarupria, University of Minnesota, All Campuses; Unveiling Cargo-Driven Dynamics in Viral Capsids through Long-Timescale Atomistic Simulations [New user identified for 5 MDs]*

MCB250010P Manfred Lindau, University of Miami; Atomistic Simulations of Munc13- and Munc18-Mediated SNARE Complex Assembly for Exocytosis [New user identified for 9 MDs]

MCB250011P Ryan Gumpper, University of North Carolina at Chapel Hill; Variant-Driven Dynamics of D2R and 5-HT2AR: A Molecular Framework for Personalized Antipsychotic Therapy [New user identified for 4.5 MDs]*

MCB250012P Wei Gao, California Institute of Technology; Generalizable in-silico wearable biosensing environment toward continuous health monitoring [New user identified for 3 MDs]*

MCB250013P Gnana Gnanakaran, Los Alamos National Laboratory; Tracking the Conformational Changes of Viral Type-1 Membrane Fusion Protein Extension [New user identified for 3 MDs]*

MCB250015P Crystal Archer, University of Arkansas; Probing the structural impacts of PKC-dependent phosphorylation of the KCNQ2 channel complex with calmodulin and phospholipid PIP2 at the plasma membrane [New user identified for 8 MDs]

MCB250017P Fatemeh Khalili-Araghi, University of Illinois Chicago; Molecular Dynamics Investigation of Claudin-2 Paracellular Channel Gating Mechanism [New user identified for 9.1 MDs]

The time allocations for the 54 proposals identified by the committee as best meeting the selection criteria for time allocations total approximately 330 MDs. Approximately 24% of MDs were allocated to 15 proposals whose PIs have not received time on Anton (identified as “new users”). Approximately 76% of the MDs were allocated to proposals from PIs who have received allocations of time on Anton in previous rounds (identified as “returning users”).

In carrying out its task, the committee identified as many promising proposals as possible and made difficult decisions on the number of allocations recommended given the constraints on the total available simulation time. The total simulation time requested by the submitted proposals was approximately 483 MDs. As a result, not every proposal could be recommended for an allocation and many interesting projects received recommendations for less than the full allocation amount.

The committee would like to thank DESRES, PSC, and all the 2025 Anton 3 applicants for the opportunity to assist in identifying the proposals best meeting the selection criteria for time allocations on the new Anton 3 machine. The committee members are universally enthusiastic about the potential advances in the field that are facilitated by Anton 3 and are looking forward to seeing the important new results from the Anton 3 users.