Report of the Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics: Eleventh Round (2020)

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¹ See Appendix C.

• 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 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 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. A member of the PSC staff was present as an observer throughout the committee’s discussions to address any additional questions that arose on Anton’s technical capabilities 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. Anton 2 allocations of 460,000 MDUs was the maximum amount of time available to a proposal. Principal investigators could also request a smaller time allocation. The committee was further asked to allocate at least 25% of the time to principal investigators 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. The committee was permitted to consider a modified time allocation if it concluded that the proposed research required a greater or smaller number of node-hours than initially requested by an applicant, up to the 460,000 MDUs maximum.

Initial reviews of the proposals were provided by the 24 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 relationships with an applicant.

The committee held its meeting online, on August 31, 2020. 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. As described in detail above, committee members considered the scientific merit, justification of the requested time, and the qualifications of the principal investigator and key personnel. The committee reviewed the slate of proposals under consideration, came to a consensus on which proposals it judged best met the selection criteria, and, in some cases, decided to suggest a modified allocation of time on Anton 2. Detailed comments for each of the 71 proposals are included in Appendix B.

The committee concluded that the proposals listed below best met the selection criteria set forth in the RFP for Biomolecular Simulation Time on Anton 2. Of these 55 proposals, 33 proposals were selected for a modified allocation (identified below with an *).

In alphabetical and numerical order by proposal submission number, the proposals judged by the committee as best meeting the selection criteria of the RFP are:

CHE100024P Kendall Houk, University of California, Los Angeles; Mechanistic Study and Engineering of MaDA Family of Enzymes to Access Bioactive Cyclohexenes [Returning user identified for 52,800 MDUs]*

CHE180044P Vincent Voelz, Temple University; Simulations to Reveal Allosteric Activation Pathways of Phenylalanine Hydroxylase [Returning user identified for 153,334 MDUs]*

IBN130013P Maria Bykhovskaia, Wayne State University; Protein Machinery Regulating Synaptic Vesicle Fusion [Returning user identified for 294,207 MDUs]

MCB100016P Aleksei Aksimentiev, University of Illinois at Urbana-Champaign; Selective Lipid Scrambling and Drug Delivery Using a DNA Enzyme [Returning user identified for 443,285 MDUs]

MCB100017P Emad Tajkhorshid, University of Illinois at Urbana-Champaign; Investigating the Molecular Mechanism Behind Prestin-Driven Outer Hair Cell Electromotility [Returning user identified for 459,091 MDUs]

MCB100018P Benoit Roux, University of Chicago; Binding Specificity of Inhibitors and Conformational Dynamics in Abl- and Src-Kinases [Returning user identified for 300,000 MDUs]*

MCB100019P Wonmuk Hwang, Texas A&M University; Role of Nonspecific Interactions for the Motion of the Kinesin Motor Near the Microtubule Track [Returning user identified for 460,000 MDUs]

MCB100024P Martin Gruebele, University of Illinois at Urbana-Champaign; Protein-Protein Binding Dynamics in the Human Cytoplasm [Returning user identified for 200,000 MDUs]*

MCB110005P Douglas James Tobias, University of California, Irvine; Atomistic Modeling of Cooperativity in the Activation of the Hv1 Proton Channel and the Regulation of Aquaporin 0 Water Permeability [Returning user identified for 230,000 MDUs]*

MCB110012P Jeffery B. Klauda, University of Maryland, College Park; Structural Study of Active and Inactive Dimerization of the PlexinA1 Intracellular Domain [Returning user identified for 460,000 MDUs]

MCB110023P Matthias Buck, Case Western Reserve University; Raf Domain Interactions and the Role of 14-3-3 Association [Returning user identified for 200,000 MDUs]*

MCB110059P Wonpil Im, Lehigh University; Ligand Activation and Modulation of TRPV2 by Internal Lipids and 2-APB [Returning user identified for 460,000 MDUs]

MCB110070P Victor S. Batista, Yale University; A Computational Approach for Discovering Novel SARS2-CoV Spike Inhibitors [Returning user identified for 170,000 MDUs]*

MCB110074P John Parkinson, University of Utah; Transmembrane Signaling Mechanisms in a Bacterial Chemoreceptor [Returning user identified for 449,890 MDUs]

MCB130045P Albert Lau, Johns Hopkins University; Allosteric Signaling Pathways in the NMDA Receptor [Returning user identified for 460,000 MDUs]

MCB130048P David Cowburn, Yeshiva University; Dynamic Interaction of Metabolic Regulator Maf1 and Pol III RNA Polymerase [Returning user identified for 460,000 MDUs]

MCB130052P Themis Lazaridis, City University of New York; Substantiating the Amyloid Pore Hypothesis in Degenerative Diseases [Returning user identified for 230,000 MDUs]*

MCB140052P Richard W. Pastor, National Institutes of Health; Enhancement of Pore Formation by Viral Fusion Peptides: Lysolipids, Surface Tension, and Spontaneous Curvature [Returning user identified for 459,400 MDUs]

MCB140062P Vladimir Yarov-Yarovoy, University of California, Davis; Multi-Microsecond Simulations of Voltage-Gated Sodium Channel Modulation by Natural and Designed Peptides [Returning user identified for 230,000 MDUs]*

MCB140063P Yuri Lyubchenko, University of Nebraska Medical Center; Role of Lipid Bilayers in the Dynamics and Misfolding of Alpha-Synuclein Protein [Returning user identified for 460,000 MDUs]

MCB160080P Michael Feig, Michigan State University; Long-Time Kinetics of Protein-Protein Interactions in Conjunction with Trp-Cys Quenching Spectroscopy Experiments [Returning user identified for 333,000 MDUs]*

MCB160087P Mahmoud Moradi, University of Arkansas at Little Rock; Characterizing pH-Triggered Activation of Influenza Hemagglutinin Protein [Returning user identified for 288,000 MDUs]*

MCB160089P Igor Vorobyov, University of California, Davis; Molecular Determinants of Multi-Target Binding of hERG Blocking Drugs for Personalized Medicine [Returning user identified for 225,000 MDUs]*

MCB170089P Lucy Forrest, National Institutes of Health; Exploring Molecular Interactions of the Human Serotonin Transporter [Returning user identified for 460,000 MDUs]

MCB170090P Chun Wu, Rowan University; In silico Visioning Communications Between Signal Ligands Bound to β2 Adrenergic G-protein Coupled Receptor (GPCR) and Effecter Guanine Nucleotide (GDP) Bound to Gα in an Open Conformation Using Molecular Dynamics Simulations in Explicit Membrane [Returning user identified for 150,000 MDUs]*

MCB170093P Hans Peter Larsson, University of Miami; Molecular Determinants of Gating in Non-swapped Topology: hERG1 and HCN Channels [Returning user identified for 230,000 MDUs]*

MCB170096P Baron Chanda, University of Wisconsin–Madison; Tripartite Cyclic Nucleotide Binding Domain/Voltage-Sensor/Pore Coupling in the Hyperpolarized Cyclic Nucleotide Gated Channel [Returning user identified for 460,000 MDUs]

MCB170106P Yun Luo, Western University; Molecular Selectivity and Saturation in a Connexin Channel [Returning user identified for 156,703 MDUs]*

MCB180076P Cristiano Dias, New Jersey Institute Technology; Effects of Lipid Bilayers on Amyloid Fibril Formation [Returning user identified for 230,000 MDUs]*

MCB180078P Xiaolin Cheng, The Ohio State University; Investigation of Structural Transitions That Govern the Function of the Virulence Factor RfaH [Returning user identified for 200,000 MDUs]*

MCB180080P Ira Kurtz, University of California, Los Angeles; Transport Mode Determinants and Their Role in Gating in the SLC4 Family [Returning user identified for 202,500 MDUs]*

MCB180081P Liqun Zhang, Tennessee Technological University; Anton Simulation on Human Beta Defensin Type 3 Interaction with Chemokine Receptor and with Lipid Membrane [Returning user identified for 230,000 MDUs]*

MCB180084P Juan Perilla, University of Delaware; Determination of the Role of Maturation Inhibitors on the Dynamical Properties of HIV Spacer Peptide 1 in Protein Assemblies [Returning user identified for 230,000 MDUs]*

MCB180087P Eric Deeds, University of California, Los Angeles; Understanding the Specificity of Key Steps in Proteasome CP Assembly [Returning user identified for 230,000 MDUs]

MCB180088P Oliver Beckstein, Arizona State University; Conformational Transition of a Secondary Transporter [Returning user identified for 189,225 MDUs]*

MCB190044P Jerome Lacroix, Western University; Opening the Mechanosensitive Piezo2 Channel [Returning user identified for 460,000 MDUs]

MCB190052P Jianhan Chen, University of Massachusetts Amherst; Gating of TMEM16A Calcium-Activated Chloride Channels [Returning user identified for 300,000 MDUs]*

MCB190057P Jose Faraldo-Gomez, National Institutes of Health; Mechanisms of Ion Conduction, Selectivity, and Inhibition of the Human Lysosomal K+ Channel TMEM175 [Returning user identified for 460,000 MDUs]

MCB190070P Alexey Ladokhin, The University of Kansas; Atomistic Modeling of Membrane-Induced Conformational Changes in Anti-Apoptotic Bcl-xL [Returning user identified for 226,500 MDUs]*

MCB200062P Qiang Cui, Boston University; Molecular Dynamics Simulation of Allosteric Transition in Tetracycline Repressor [New user identified for 217,120 MDUs]*

MCB200067P L. Michel Espinoza-Fonseca, University of Michigan; Atomic-Level Mechanisms for Regulation of Calcium Transport in the Heart [New user identified for 225,223 MDUs]*

MCB200071P Denise Okafor, The Pennsylvania State University; The Nature of Interdomain Interactions in the Farnesoid X Receptor [New user identified for 200,000 MDUs]*

MCB200075P Cheng Zhu, Georgia Institute of Technology; MD Simulations of Spike Headpiece Kinetics During SARS-CoV-2 Viral Entry [New user identified for 445,094 MDUs]

MCB200076P James McCarty, Western Washington University; Dynamic Conformational Selection in the Prion-Like Propagation of Tauopathies [New user identified for 200,000 MDUs]*

MCB200078P Rui Sun, University of Hawaii at Manoa; Characterization of Synaptic Vesicle and Its Interaction with Alpha-Synuclein [New user identified for 319,317 MDUs]

MCB200080P Andrew Ward, The Scripps Research Institute; Investigating the Anion Selectivity of a Novel Mechanically Activated Ion Channel [New user identified for 230,000 MDUs]*

MCB200082P Shivangi Nangia, North Dakota State University; Disruption of Bacterial Persister Cells by Antimicrobial Peptides (AMPs): Understanding Effects Length of Cationic AMPs [New user identified for 114,217 MDUs]*

MCB200085P Jing Li, The University of Mississippi; Slow Inactivation in a Voltage-Gated Sodium Channel [New user identified for 345,000 MDUs]*

MCB200087P Paul Robustelli, Dartmouth College; Characterizing the Binding Mechanisms of Castration-Resistant Prostate Cancer Therapeutics to the Intrinsically Disordered N-terminal Domain of the Androgen Receptor [New user identified for 460,000 MDUs]

MCB200088P Erika Taylor, Wesleyan University; Targeting Protein Conformational Changes to Develop Dynamic Disruptors for the Treatment of Gram-Negative Bacterial Infections [New user identified for 150,000 MDUs]*

MCB200090P Eleonora Gianti, Temple University; Unraveling Viral RdRp Dynamics to Understand SARS-CoV-2 Replication and Enable Drug Repurposing and Novel Therapeutic Design [New user identified for 262,000 MDUs]

MCB200093P Viviana Monje-Galvan, University at Buffalo; Protein-Lipid Interactions in Cellular Signaling in Cancer [New user identified for 230,000 MDUs]*

MCB200095P Taras Pogorelov, University of Illinois at Urbana-Champaign; Membrane Signaling Dynamics in Mammalian Cytoplasm [New user identified for 227,475 MDUs]*

MCB200098P Steve Reichow, Portland State University; Mechanisms of Electrical Coupling and Ion-Selectivity by Connexin-46 and Connexin-50 Intercellular Gap Junctions [New user identified for 227,100 MDUs]

MCB200099P Moitrayee Bhattacharyya, Yale University; Conformational Landscape of the Intrinsically Disordered Regions in Dyrk3 and Their Interactions with the Kinase Domain [New user identified for 152,031 MDUs]

The time allocations for the 55 proposals identified by the committee as best meeting the selection criteria for time allocations total approximately 15,800,000 MDUs. Approximately 25.2% MDUs were allocated to proposals whose principal investigators have not received time on Anton (identified as “new users”). Approximately 74.8% of the MDUs are allocated to proposals from principal investigators 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 given the constraints on the total available simulation time. The total simulation time requested by the submitted proposals was more than 29,675,904 MDUs. As a result, a number of interesting proposals were not able to be recommended in this round, entailing difficult decisions.

The committee would like to thank DESRES, PSC, and all of the 2020 Anton 2 applicants for the opportunity to assist in identifying the proposals best meeting the selection criteria for time allocations on the Anton machine. The committee members were universally enthusiastic about the potential advances in the field that are facilitated by Anton 2 and are looking forward to seeing the important new results from the Anton users.

Sincerely,

Ivet Bahar

Chair, Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics, Eleventh Round