Report of the Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics,
Committee on Proposal
Evaluation for Allocation of Supercomputing
Time for the
Study of Molecular Dynamics, Ninth Round
Board on Life Sciences
Board on Chemical Sciences and Technology
Division on Earth and Life Studies
A Consensus Study Report of
THE NATIONAL ACADEMIES PRESS
October 15, 2018
Jodi Swidzinski Hezky, Ph.D.
D. E. Shaw Research
120 West 45th Street, 39th Floor
New York, NY 10036
Dear Dr. Hezky:
This letter describes the work and transmits the final report of the Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics, Ninth Round.
The committee evaluated submissions received in response to a Request for Proposals (RFP) for Biomolecular Simulation Time on Anton 2, a supercomputer designed and built by D. E. Shaw Research (DESRES). Over the past 8 years, DESRES has made an Anton or Anton 2 system housed at the Pittsburgh Supercomputing Center (PSC) available to the non-commercial research community, based on the advice of previous National Research Council committees. As in those prior rounds, the goal of the ninth RFP for simulation time on Anton 2 is to continue to facilitate breakthrough research in the study of biomolecular systems by providing a massively parallel system specially designed for molecular dynamics simulations. These capabilities allow multi-microsecond 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 2 machine housed at PSC available for approximately 15,800,000 molecular dynamic units (MDUs) over the period following November 2018, and DESRES asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to once again facilitate the allocation of time to the non-commercial community. The work of the committee to evaluate proposals for time allocations was supported by a contract between D. E. Shaw Research and the National Academy of Sciences and was performed under the auspices of the National Academies’ Board on Life Sciences.
To undertake this task, the National Academies convened a committee of experts to evaluate the proposals submitted in response to the RFP. The committee of 19 was chaired by Dr. Angel Garcia, Director of the Center for Nonlinear Studies at Los Alamos National Laboratory. The committee members were selected for their expertise in molecular dynamics simulations and experience in the subject areas represented in the 72 proposals considered. The members comprised a cross-section of the biomolecular dynamics field in academia, industry, and government, including both senior and junior investigators.
The Anton 2 RFP described the three criteria against which the committee was asked to evaluate proposals:
- Scientific Merit, including the potential to advance understanding on an important problem or question in the field; 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 approach to the proposed studies.
- Justification for Requested Time Allocation, including a clear and well-justified need for time on Anton rather than conventional supercomputers; and 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 with molecular simulations, past publications and demonstrated progress from previous Anton allocations.
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 whether 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 time allocations of 460,000 MDUs was the maximum amount of time available to a proposal. Principal investigators (PIs) could also request a lesser time allocation. The committee was further asked to allocate at least 25% of the 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. The committee was permitted to consider a modified time allocation if it concluded that the proposed research required a greater or lesser number of node-hours than initially requested by an applicant.
Initial reviews of the proposals were provided by the 19 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 in Washington, DC, on August 7, 2018. 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 qualifications of the PI and key personnel. The committee considered 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 72 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 57 proposals, 40 proposals were selected for a modified allocation (identified below with an *).
In numerical order by proposal submission number, the proposals judged by the committee as best meeting the selection criteria of the RFP are:
PSCA18002P Cristiano Dias, New Jersey Institute of Technology; Role of Magnesium on the Allosteric Effect of the Circadian Clock Protein KaiC [New user identified for 156,796 MDUs]*
PSCA18003P Harel Weinstein, Weill Cornell Medicine of Cornell University; Dynamic Remodeling of Lipid Nanodiscs Determined by Functionally Diverse States Identified in Cryo-EM Structures of a TMEM16 Scramblase [Returning user identified for 460,000 MDUs]
PSCA18004P Rosa Di Felice, University of Southern California; Elucidating the Structure and Dynamics of Class 2 CRISPR/Cas9 Ternary Complexes by Molecular Dynamics (MD) Simulations [New user identified for 100,000 MDUs]* PSCA18005P Maria Bykhovskaia, Wayne State University; Protein Machinery Regulating Synaptic Vesicle Fusion [Returning user identified for 230,000 MDUs]*
PSCA18006P Wonpil Im, Lehigh University; Molecular Mechanisms of Ligand-Induced TRPV2 Channel Activation [Returning user identified for 460,000 MDUs]
PSCA18007P Jerome Lacroix, Western University of Health Sciences; Gating Mechanisms of the Mechanosensitive Piezo1 Channel [Returning user identified for 460,000 MDUs]
PSCA18008P Xiaolin Cheng, The Ohio State University; Investigation of Conformational Dynamics Involved in Genome Editing Events by CRISPR-Cpf1 [New user identified for 230,000 MDUs]*
PSCA18009P Krzysztof Palczewski, Case Western Reserve University; The Molecular Basis of hERG Potassium Ion Channel Inhibition and Activation [Returning user identified for 100,000 MDUs]*
PSCA18010P Themis Lazaridis, City College of New York; Membrane Pore Formation by Peptides and Toxins [Returning user identified for 460,000 MDUs]
PSCA18011P Jeffery Klauda, University of Maryland; Unraveling the Structure-Function Relationship of the Serotonin Receptor (5HT3) [Returning user identified for 230,000 MDUs]*
PSCA18012P Peter C. Searson, Johns Hopkins University; The Transport of Neurotoxicant Antidotes Across the Blood–Brain Barrier [Returning user identified for 180,000 MDUs]*
PSCA18013P Yuri Lyubchenko, University of Nebraska Medical Center; Interactions and Misfolding of Amyloid Beta (Aβ) Proteins in Presence of Lipid Bilayers [Returning user identified for 230,000 MDUs]*
PSCA18016P Stephen Wassall, Indiana University–Purdue University Indianapolis; Do Vitamin E and Polyunsaturated Phospholipids Co-Localize? [New user identified for 130,000 MDUs]*
PSCA18018P Vladimir Yarov-Yarovoy, University of California, Davis; Exploring Sodium Channel Drug Modulation with Multi-Microsecond Simulations [Returning user identified for 265,700 MDUs]*
PSCA18019P Wenwei Zheng, Arizona State University; Investigating the Molecular Interactions Controlling the Liquid Droplet Formation by Intrinsically Disordered Proteins [Returning user identified for 230,000 MDUs]*
PSCA18020P Michael Grabe, University of California, San Francisco; Mechanistic Insight on Anion Transporters [Returning user identified for 230,000 MDUs]*
PSCA18022P Andrew Pohorille, University of California, San Francisco; Computational Electrophysiology of Pentameric Ligand Gated Ion Channels [Returning user identified for 230,000 MDUs]*
PSCA18023P Edward Lyman, University of Delaware; Towards a “Gold-Standard” Dataset for GPCR-Cholesterol Interactions: Subfamily Specific Cholesterol Interaction Sites [Returning user identified for 143,878 MDUs]*
PSCA18025P Baron Chanda, University of Wisconsin; Non-Canonical Voltage-Sensor Pore Coupling in the Hyperpolarized Cyclic Nucleotide Gated Channel [Returning user identified for 230,000 MDUs]*
PSCA18026P Ira Kurtz, University of California, Los Angeles (UCLA); Gating and Ion Transport Mechanisms in SLC4 Family [New user identified for 150,000 MDUs]*
PSCA18027P Matthias Buck, Case Western Reserve University; The Signaling Mechanism of EphA2 and K-Ras at Membranes [Returning user identified for 300,000 MDUs]*
PSCA18029P Victor Batista, Yale University; Towards Understanding Electron Transport Pathways of Conductive Geobactor Pili and Design Principle for Enhancement of Their Conductivity [Returning user identified for 65,000 MDUs]*
PSCA18030P Alfredo Angeles-Boza, University of Connecticut; Membrane Penetration by Antimicrobial Peptide Bound to Zn2+: Understanding the Influence of Zn2+ Ions on the Helicity and Possible Oligomerization [New user identified for 374,000 MDUs]*
PSCA18032P Liqun Zhang, Tennessee Technological University; Anton Simulation on Human Beta Defensin Type 3 Interaction with Chemokine Receptor and with Lipid Membrane [New user identified for 200,000 MDUs]*
PSCA18033P Paul Axelsen, University of Pennsylvania; Amyloid Fibril Nucleation in the Reverse Micelle Nanoenvironment [Returning user identified for 303,600 MDUs]*
PSCA18034P Martin Gruebele, University of Illinois at Urbana-Champaign; Protein Folding in Simulated Bacterial and Mammalian Cytosol Models [Returning user identified for 460,000 MDUs]
PSCA18035P Alexey Onufriev, Virginia Tech; Large-Scale Conformational Transitions in the Nucleosome [New user identified for 230,000 MDUs]*
PSCA18036P Juan de Pablo, The University of Chicago; Structural and Dynamical Characterization of Chemically Diverse Polysaccharides in Aqueous Solution [New user identified for 100,000 MDUs]*
PSCA18037P Albert Lau, Johns Hopkins University School of Medicine; Ligand-Binding Processes in Glutamate Receptors [Returning user identified for 460,000 MDUs]
PSCA18038P Kendall N. Houk, University of California, Los Angeles; Understanding and Engineering the NasB Enzyme for the Biosynthesis of New Synthetically Valuable Diketopiperazine Dimers [Returning user identified for 216,000 MDUs]*
PSCA18040P Rommie Amaro, University of California, San Diego; Investigating Full-Length p53 Tetramer Dynamics and Druggability by Ensemble-Based Approaches [Returning user identified for 460,000 MDUs]
PSCA18041P David Cowburn, Albert Einstein College of Medicine; FG Repeats Domain Interactions of the Nuclear Pore by Simulation and Experiment [Returning user identified for 230,000 MDUs]*
PSCA18042P Gregory Voth, The University of Chicago; Molecular Mechanisms in HIV-1 Membrane Targeting and Restriction [Returning user identified for 370,000 MDUs]*
PSCA18043P Juan Perilla, University of Delaware; Elucidating the Molecular Interactions Between the HIV-1 Capsid and Human Cofactors FEZ1 and MxB [New user identified for 230,000 MDUs]*
PSCA18045P Ron Dror, Stanford University; Revealing the Structural Basis of Photoactivation to Enable the Design of Superior Optogenetics Tools [Returning user identified for 460,000 MDUs]
PSCA18046P Richard Pastor, National Institutes of Health; The Interaction of Lecithin: Cholesterol Acyltransferase and Nascent High-Density Lipoprotein [Returning user identified for 460,000 MDUs]
PSCA18050P Paulette Clancy, Cornell University; Towards the Computational Selection of Oligothioetheramides Capable of Selectively Maximizing Bacterial Cell Membrane Disruption While Minimizing Mammalian Cell Membrane Interactions [New user identified for 100,000 MDUs]*
PSCA18051P Benoît Roux, The University of Chicago; Binding Specificity of Inhibitors and Conformational Dynamics in Abl- and Src-Kinases [Returning user identified for 300,000 MDUs]*
PSCA18052P Maria Kurnikova, Carnegie Mellon University; Characterizing Mechanisms of the Glutamate Receptor – the Lock in the Interneuronal Communication Highway [Returning user identified for 460,000 MDUs]
PSCA18053P Michael Feig, Michigan State University; Interactions of Drug-Like Small Molecules with Crowded Cell-Like Environments [Returning user identified for 460,000 MDUs]
PSCA18055P Jeetain Mittal, Lehigh University; Elucidating the Solvation Effects in Protein Liquid-Liquid Phase Separation [Returning user identified for 300,264 MDUs]*
PSCA18056P Alemayehu Gorfe, The University of Texas Medical School at Houston; Membrane Orientation Dynamics of Lipidated Small GTPases [Returning user identified for 300,000 MDUs]*
PSCA18061P Gaurav Arya, Duke University; Long Timescale Simulations of Viral DNA Packaging Motors [New user identified for 432,770 MDUs]*
PSCA18062P Wenjun Zheng, State University of New York at Buffalo; Molecular Dynamics Simulation of the Activation Mechanism of NMDA Receptors [Returning user identified for 230,000 MDUs]*
PSCA18063P Vincent Voelz, Temple University; Simulation of ACT Domain Dimerization and Allosteric Activation of Phenylalanine Hydroxylase [New user identified for 100,000 MDUs]*
PSCA18065P Eric Deeds, University of Kansas; Understanding the Separation of Time Scales in Proteasome Assembly [New user identified for 230,000 MDUs]*
PSCA18067P Shikha Nangia, Syracuse University; Role of S-Palmitoylation on the Blood–Brain Barrier Tight Junction Interface [Returning user identified for 120,000 MDUs]*
PSCA18068P Oliver Beckstein, Arizona State University; Conformational Transition of a Secondary Transporter [Returning user identified for 459,545 MDUs]
PSCA18069P Emad Tajkhorshid, University of Illinois; Structural Dynamics Underlying Protein-Protein Interactions and Signaling in Wildtype and Oncogenic K-Ras [Returning user identified for 300,000 MDUs]*
PSCA18070P Michael Levitt, Stanford University; Understanding the Role of Post-Translational Modifications on the Binding of Chemokine Receptors to Chemokines [New user identified for 460,000 MDUs]
PSCA18071P John Straub, Boston University; Observation of Stable Phase Separation and Domain Partitioning of C99 Transmembrane Domain in and Atomistic Ternary Membrane Mixture [New user identified for 230,000 MDUs]
PSCA18072P Douglas Tobias, University of California, Irvine; Atomistic Modeling of Eye Lens Proteins: γ-Crystallins and Aquaporin 0 [Returning user identified for 300,000 MDUs]*
PSCA18074P William Goddard, California Institute of Technology; Structures and Mechanism for Activation of the Class C-GPCRs Through MD Simulations [New user identified for 227,475 MDUs]*
PSCA18076P Eduardo Perozo, The University of Chicago; C-Type Inactivation in a Voltage-Gated Potassium Channel [Returning user identified for 230,000 MDUs]*
PSCA18077P Igor Vorobyov, University of California, Davis; Molecular Determinants of hERG Channel Facilitation Effects by hERG Blocking Drugs [Returning user identified for 378,000 MDUs]*
PSCA18078P Mahmoud Moradi, University of Arkansas; Deciphering Lipid Modulation of Transmembrane Protein Conformational Dynamics [Returning user identified for 160,000 MDUs]*
PSCA18079P Kerwyn Huang, Stanford University; Connecting Conformational Changes Due to Membrane Binding with Geometry Sensing of the Bacterial Actin Homolog MreB [Returning user identified for 227,000 MDUs]
The time allocations for the 57 proposals identified by the committee as best meeting the selection criteria for time allocations total approximately 15,800,000 MDUs. Approximately 23.3% of the MDUs were allocated to proposals whose PI have not received time on Anton. Approximately 76.7% of the MDUs were allocated to proposals from 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 28,821,640 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 D. E. Shaw Research, the Pittsburgh Supercomputing Center, and all of the 2018 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 facilitated by Anton 2 and are looking forward to seeing the important new results from the Anton users.
Chair, Committee on Proposal Evaluation for Allocation of Supercomputing Time for the Study of Molecular Dynamics, Ninth Round
|cc:||Dr. Phillip Blood, Pittsburgh Supercomputing Center|
|Dr. Gregory Symmes, National Academies of Sciences, Engineering, and Medicine|
|Dr. Frances Sharples, National Academies of Sciences, Engineering, and Medicine|
A. Table 1: Proposals Reviewed by the Committee*
B. Individual Proposal Summary Evaluations*
*These appendices are not available to the public.
The committee used the points below to help guide its review of the proposals. The reviewers were asked to comment on the strengths and weaknesses of the proposals by considering the following:
Level of scientific merit. This should be evaluated by considering:
- Potential to advance understanding of an important problem or question in the field; potential for breakthrough science resulting in new discoveries and understanding
- Impact that successful completion of the proposed research would have on the knowledge, methods, and current barriers in the field
- Project is scientifically and technologically feasible with clear, well-developed, and appropriate goals, objectives, and approach to the proposed studies
Justification for requested time allocation. This should be evaluated by considering:
- Clear and well-justified need for time on Anton rather than conventional supercomputers
- 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. This should be evaluated by considering:
- Appropriate experience and training to successfully conduct the proposed studies
- Evidence of knowledge and prior experience with molecular simulations
- Past publications and demonstrated progress from previous Anton allocations
ROSTER AND BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS
COMMITTEE ON PROPOSAL EVALUATION FOR ALLOCATION OF SUPERCOMPUTING TIME FOR THE STUDY OF MOLECULAR DYNAMICS, NINTH ROUND
ANGEL GARCIA, Los Alamos National Laboratory
NATHAN BAKER, Pacific Northwest National Laboratory
JEROME BAUDRY, The University of Alabama in Huntsville
JAMES BRIGGS, University of Houston
LYLE D. BURGOON, U.S. Army Engineer Research and Development Center
ANDREW FERGUSON, The University of Chicago
ALAN GROSSFIELD, University of Rochester Medical Center
JAMES C. GUMBART, Georgia Institute of Technology
WONMUK HWANG, Texas A&M University
MARGARET JOHNSON, Johns Hopkins University
FATEMEH KHALILI-ARAGHI, University of Illinois at Chicago
ERIC MAY, University of Connecticut
CLARE MCCABE, Vanderbilt University
YINGLONG MIAO, University of Kansas
CAROL B. POST, Purdue University
SADASIVAN SHANKAR, Harvard University
ERIKA TAYLOR, Wesleyan University
CHUNG WONG, University of Missouri–St. Louis
YAROSLAVA G. YINGLING, North Carolina State University
ANDREA HODGSON, Project Director, Board on Life Sciences
ANNA SBEREGAEVA, Associate Program Officer, Board on Chemical Sciences and Technology
ANGELA KOLESNIKOVA, Senior Program Assistant, Board on Life Sciences
KEEGAN SAWYER, Senior Program Officer, Board on Life Sciences
BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS
Angel Garcia, PhD, is currently the Director of the Center for Nonlinear Studies at Los Alamos National Laboratory. Previously he was the Department Head of the Physics, Applied Physics, and Astronomy Department at Rensselaer Polytechnic Institute (RPI). He was also a Professor of Physics and the Senior Constellation Chaired Professor of Biocomputation and Bioinformatics at RPI. Dr. Garcia’s research group focuses on the use of theoretical and computational methods to study aspects related to biomolecular dynamics and statistical mechanics. Its main research objectives are to understand the folding, dynamics, and stability of biomolecules. His group’s research interests include the hydrophobic effect, enzyme catalysis, nucleic acid structure and dynamics, RNA folding, electrostatics, protein hydration, and peptide interactions with membranes. Dr. Garcia received a PhD in Theoretical Physics from Cornell University. He is a fellow of the American Physical Society and a member of the Biophysical Society, The Protein Society, the American Association for the Advancement of Science, and the American Chemical Society. He received the Edward Bouchard prize of the American Physical Society in 2006. Dr. García is an Associate Editor of Proteins: Structure, Function, and Bioinformatics, a member of the editorial board of the Biophysical Journal and Molecular Simulation, and a member of the Faculty of 1000 for BioMed Central.
Nathan Baker, PhD, is the Director for the Advanced Computing, Mathematics & Data Division at Pacific Northwest National Laboratory and a Visiting Faculty member in the Brown University Division of Applied Mathematics. His research focuses on developing new algorithms and mathematical methods in biophysics, nanotechnology, and informatics. His research projects include computational methods for modeling solvation in biomolecular systems, mathematical methods for mesoscale materials modeling, and the development of methods for signature discovery. Dr. Baker has served on review panels for various agencies, including as a member of the National Institutes of Health’s Macromolecular Structure and Function D study section. He currently is an editorial board member for Biophysical Journal and serves on the editorial board for the Nature Publishing Group’s Scientific Data. Dr. Baker is a Fellow of the American Association for the Advancement of Science and has been awarded the Hewlett-Packard Junior Faculty Excellence Award by the American Chemical Society, the National Cancer Institute caBIG Connecting Collaborators Award, and an Alfred P. Sloan Research Fellowship. He earned his doctorate in physical chemistry from the University of California, San Diego.
Jerome Baudry, PhD, is the Pei-Ling Chan Professor of Biological Sciences, Department of Biological Sciences, The University of Alabama in Huntsville (UAH). Dr. Baudry obtained his PhD in Molecular Biophysics with the highest honors from the University of Paris, UPMC/Sorbonne Universities, France. He subsequently joined the group of Klaus Schulten at the University of Illinois at Urbana-Champaign as a postdoc. After his postdoctoral work, Dr. Baudry worked in the pharmaceutical industry as a Research Scientist, and then accepted a Senior Research Scientist position back in Illinois on a non-tenure track research faculty position. Dr. Baudry joined the University of Tennessee (UT), Knoxville, and the UT/Oak Ridge National Laboratory Center for Molecular Biophysics as a tenure track Assistant Professor in 2008. In 2014, he was promoted to Associate Professor with tenure. In August 2017, Dr. Baudry joined UAH as the Pei-Ling Chan Professor. At UAH, Dr. Baudry’s group develops and applies methods and protocols for computational drug discovery, both on small molecules and biologicals, within academic, national laboratories, and industrial collaborations.
James Briggs, PhD, is an Associate Professor within the Biology and Biochemistry Department at the University of Houston. Dr. Briggs received his PhD in Chemistry from Purdue University. His research
focuses on computational studies of protein structure and function, inhibitor design, investigations of possible inhibitor resistance pathways, and the development of methods for the above project areas. Targets for these studies include those important in the treatment of AIDS, cancer, bacterial infections, and other disease states. In addition, Dr. Briggs works on inhibitors to aid in biowarfare defense (botulinum neurotoxin, anthrax toxin, and cholera toxin). Dr. Briggs’s research is focused in the highly interdisciplinary and collaborative area of computational chemistry/biochemistry. He develops and applies computational methods to problems of chemical and biochemical interest. His research falls into two general categories: computer-aided inhibitor design/discovery and computational biophysics. His main target areas in the inhibitor/ligand area are Rho kinase 1 (heart disease), PTEN (cancer), PTEN/5HTC2C (addiction control), BCL2 (cancer), and gluconeogenesis and glucose uptake (cancer); those for the computational biophysics area include cholera toxin, biofilm control, RNA structure prediction, protein electrostatics and pKa predictions, and identification of protein/enzyme function from structure only.
Lyle D. Burgoon, PhD, leads the Artificial Intelligence to Drive the Military Environment research program at the U.S. Army Engineer Research and Development Center, part of the U.S. Army Corps of Engineers. A portion of Dr. Burgoon’s research is focused on developing machine learning models that can predict the molecular interaction of chemicals found within the operational environment with human and animal proteins in order to predict toxicological or pharmacological outcomes. This work uses a combination of molecular docking, computer vision, more traditional machine learning, and deep learning approaches to make accurate predictions of whether a chemical will interact with a protein, how it will interact, and at what concentrations these interactions will lead to biological changes. This is part of Dr. Burgoon’s work that is focused on giving military intelligence operatives and strategic leaders the information they need to better understand and anticipate potential adversity and risks in the operational environment. Prior to joining the U.S. Army, Dr. Burgoon was a Senior Leader, Risk Assessor, and Science and Policy Advisor at the U.S. Environmental Protection Agency. Dr. Burgoon earned his AB cum laude in Biology and Pre-Medicine from Augustana College, Rock Island, Illinois, and his PhD in Pharmacology and Toxicology with Environmental Toxicology from the College of Veterinary Medicine at Michigan State University.
Andrew Ferguson, PhD, is an Associate Professor at the Institute for Molecular Engineering (IME) at The University of Chicago. He earned an M.Eng. in Chemical Engineering from Imperial College London in 2005, and a PhD in Chemical and Biological Engineering from Princeton University in 2010. From 2010 to 2012 he was a postdoctoral Fellow of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology (MIT) and Harvard in the Department of Chemical Engineering at MIT. He commenced his independent career in the department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign (UIUC) in August 2012 and was promoted to Associate Professor of Material Science and Engineering and Associate Professor of Chemical and Biomolecular Engineering in January 2018. He joined the IME in June 2018. Dr. Ferguson’s research uses computation and theory to understand and design self-assembling materials, macromolecular folding, and antiviral therapies. In his materials work, he applies nonlinear manifold learning to all-atom and coarse-grained simulations of polymers, peptides, and colloids to determine folding and assembly mechanisms and rational design principles. In his virology work, he developed a statistical inference procedure to translate viral sequence databases into empirical models of fitness and rationally design vaccine immunogens against HIV and hepatitis C virus. In his enhanced sampling work, he combines tools from dynamical systems theory and nonlinear manifold learning to recover folding landscapes from experimentally accessible molecular observables and uses tools from deep learning for on-the-fly collective variable identification and accelerated recovery of molecular free energy landscapes in molecular simulation. Dr. Ferguson is the recipient of a 2017 UIUC College of Engineering Dean’s Award for Excellence in Research, 2016 American Institute of Chemical Engineers Computational Molecular Science & Engineering Forum Young Investigator Award for Modeling & Simulation, 2015 American Chemical Society (ACS) OpenEye Outstanding Junior Faculty Award, 2014 National Science Foundation CAREER Award, 2014 ACS
Petroleum Research Fund Doctoral New Investigator, and was named the 2013 Institution of Chemical Engineers North American Young Chemical Engineer of the Year.
Alan Grossfield, PhD, received his undergraduate degree in Physics and Biology from Cornell University, followed by PhD work in Biophysics at Johns Hopkins University in the lab of Dr. Thomas Woolf, where he worked on molecular dynamics simulations of membranes and membrane-bound peptides. He then did a postdoc at Washington University in St. Louis in the lab of Dr. Jay Ponder, applying sophisticated polarizable force fields to the study of ion solvation. He left St. Louis for IBM Research in 2004, and spent 3 years as part of the Blue Gene team there. During that time, his research was focused on all-atom simulations of rhodopsin, with particular emphasis on the role of lipid-protein interactions in modulating rhodopsin function. In 2007, he took a faculty position in the Department of Biochemistry & Biophysics at the University of Rochester Medical Center. Since then, Dr. Grossfield’s group has continued to focus on lipid-protein interactions, including work on G-protein-coupled receptors and antimicrobial lipopeptides, using a combination of all-atom, coarse-grained, and structure-based models. More recently, his group has begun work to understand the mechanism of amyloid formation in alpha-synuclein.
James C. (JC) Gumbart, PhD, is an Associate Professor of Physics at the Georgia Institute of Technology (Georgia Tech) in Atlanta, Georgia. He obtained his BS from Western Illinois University in 2003 and his PhD in Physics from the University of Illinois at Urbana-Champaign in 2009 under the mentorship of Klaus Schulten, focusing on the area of computational biophysics. After 2 years as a postdoctoral fellow at Argonne National Laboratory working with Benoit Roux, he started his lab at Georgia Tech in early 2013. His lab carries out molecular dynamics simulations aimed primarily at understanding the composition, construction, and function of the Gram-negative bacterial cell envelope.
Wonmuk Hwang, PhD, is an Associate Professor in the Department of Biomedical Engineering at Texas A&M University. He obtained a PhD in physics from Boston University. Dr. Hwang studies the dynamics of biomolecules that carry out essential functions in the human body, for which he uses computer simulation and theoretical analysis as his main research modality. Biomolecular simulation utilizing supercomputers plays an increasingly important role in frontier biomedical research.
Margaret Johnson, PhD, joined the Biophysics faculty at Johns Hopkins University in 2013. She received her BS in Applied Math from Columbia University and her PhD in Bioengineering from the University of California, Berkeley. She completed postdoctoral training in the Laboratory of Chemical Physics at the National Institutes of Health in Bethesda, Maryland. Her research focuses on understanding how the individual interactions among thousands of diverse components in the cell generate order and collective function at the right time and the right place. She develops theoretical and computational approaches to study the evolution and mechanics of dynamic systems of interacting and assembling proteins.
Fatemeh Khalili-Araghi, PhD, specializes in theoretical and computational studies of ion channels at the University of Illinois at Chicago (UIC) as an Assistant Professor. She obtained her BS in Physics from the Sharif University of Technology in 2001 and her PhD from the University of Illinois at Urbana-Champaign in 2010. She was a postdoctoral scholar at The University of Chicago from 2010 to 2013, where she continued studies of membrane proteins with a focus on the NaK ATPase using computational modeling techniques, as well as molecular dynamics simulations. Her research at UIC will continue focusing on theoretical and computational studies of membrane proteins.
Eric May, PhD, is an Assistant Professor at the Department of Molecular and Cell Biology at the University of Connecticut. He obtained his PhD from the University of Florida in Biophysics and Biochemistry. His research interests are in the general area of computational and theoretical biophysics and biochemistry, with emphasis toward understanding conformational/phase transitions and the mechanical and thermodynamic properties of biological materials.
Clare McCabe, PhD, received her bachelor’s and PhD degrees in Chemistry from the University of Sheffield. After postdoctoral and research faculty appointments at the University of Tennessee, she joined the Colorado School of Mines faculty as an Assistant Professor of Chemical Engineering in January 2002. In 2004 she moved to Vanderbilt University, where she is now the Cornelius Vanderbilt Professor of Engineering and Professor of Chemical and Biomolecular Engineering. She is also the Associate Dean of the Graduate School and the Director of the Office of Postdoctoral Affairs. Her research interests focus on the use of molecular modeling techniques to understand and predict the thermodynamic and transport properties of complex fluids and materials. Dr. McCabe has published more than 100 papers in archival journals and presented numerous invited and contributed talks at national and international conferences. She is a fellow of the Royal Society of Chemistry and recently received the American Institute of Chemical Engineers Computational Molecular Science and Engineering Forum Impact Award.
Yinglong Miao, PhD, is an Assistant Professor in the Department of Molecular Biosciences and the Center for Computational Biology at the University of Kansas. Dr. Miao obtained his PhD in Computational Chemistry in the lab of Peter Ortoleva at Indiana University. His graduate work was focused on all-atom multi-scale modeling of infectious viruses and other bionanosystems. He subsequently began his postdoctoral research with Jeremy Smith and Jerome Baudry at the University of Tennessee and Oak Ridge National Laboratory. There, he combined the world-class experimental (neutron scattering and nuclear magnetic resonance) and supercomputing resources to investigate the structural dynamics and function of protein enzymes responsible for drug metabolism. Dr. Miao then moved to Andy McCammon’s lab at the Howard Hughes Medical Institute and University of California, San Diego, where he worked on both method developments and cutting-edge applications in accelerated biomolecular simulations and drug discovery of G-protein-coupled receptors. Dr. Miao develops novel theoretical and computational methods with applications in protein folding, molecular recognition, cellular signaling, and computer-aided drug design.
Carol B. Post, PhD, is a Professor of Medicinal Chemistry and Molecular Pharmacology and a Professor of Biomedical Engineering at Purdue University. She specializes in Computational Chemistry and Biological Nuclear Magnetic Resonance (NMR) and is also a National Institutes of Health principal investigator. Since 1990, she has directed a research program aimed toward understanding protein structure and the molecular mechanisms that regulate molecular interactions and enzymatic activity. Her research program utilizes primarily computer simulation methods and NMR spectroscopy to study the structure and function of proteins and protein complexes associated with signaling, with current efforts being focused on Src and Syk tyrosine kinase. Molecular dynamics simulation methods and NMR spectroscopy are the approaches taken to study proteins and protein complexes associated with cancer and human viruses. Dr. Post is an internationally recognized leader in the regulation and function of protein–protein interactions associated with cell signaling and viruses. Dr. Post was recognized with the Lions Club Award for Outstanding Achievements in Cancer Research in 2009, the Chaney Faculty Scholar Award from the College of Pharmacy in 2013, and the Provost’s Award for Outstanding Graduate Mentor in 2016.
Sadasivan Shankar, PhD, is the first Margaret and Will Hearst Visiting Lecturer in Computational Science and Engineering at the Harvard School of Engineering and Applied Sciences. In Fall 2013 as the first Distinguished Scientist in Residence at the Institute of Applied Computational Science at Harvard, along with Dr. Tim Kaxiras, he developed and co-instructed with Dr. Brad Malone a graduate-level class on Computational Materials Design, which covered fundamental atomic and quantum techniques and practical applications for new materials by design. Dr. Shankar earned his PhD in Chemical Engineering and Materials Science from the University of Minnesota, Minneapolis. Dr. Shankar has initiated and led multiple efforts in Intel, most recently the Materials Design Program. Over his tenure in research and development in the semiconductor industry, he and his team worked on several new initiatives, including using modeling to optimize semiconductor processing and equipment for several technology generations,
advanced process control using physics-based models, thermo-mechanical reliability of microprocessors, thermal modeling of 3D die stacking, and using thermodynamic principles to estimate energy efficiency of ideal computing architectures. At Harvard, Dr. Shankar is involved in teaching and research in the areas of large-scale computational methods, chemistry, materials, and in translational ideas.
Erika Taylor, PhD, has been investigating problems and finding solutions at the interface of chemistry and biology. During her undergraduate years she worked on the synthesis of natural product analogue inhibitors for a protein phosphatase that was important for the treatment of cancer. As a graduate student, she trained extensively in biochemistry, specializing in functional assignment to previously uncharacterized proteins, which gave her the tools to understand enzyme mechanisms and the impact of evolutionary context on the workings of proteins. During her postdoctoral training period, she applied all she learned while earning her earlier degrees to the discovery and characterization of inhibitors of nucleotide metabolism, which are still being investigated as potential medicines to thwart malaria, a disease that kills more than 500,000 people in the world each year. As a faculty member at Wesleyan University, her projects have focused on the identification and characterization of enzymes that (1) are important for the development of antimicrobials for the treatment of Gram-Negative bacterial infections (with an emphasis on bacteria that cause food-borne illnesses including E. coli, Salmonella, and V. cholerae); and (2) could improve the efficiency of biomass to biofuel conversion, particularly the breakdown and bacterial utilization of lignin. Dr. Post earned an honors Chemistry undergraduate degree from the University of Michigan and her PhD in Chemistry from the University of Illinois at Urbana-Champaign. After a postdoctoral position at the Albert Einstein College of Medicine she began to teach and perform research at Wesleyan University.
Chung Wong, PhD, is a Professor within the Department of Chemistry and Biochemistry at the University of Missouri–St. Louis. He received his BSc (Hons.) degree from the Chinese University of Hong Kong and his PhD degree from The University of Chicago. He completed his postdoctoral work at the University of Houston. His laboratory’s research involves the development and applications of computational methods to study biomolecular structure, dynamics, and function and to aid the design of bioactive compounds. Dr. Wong has held academic and industrial positions at the University of Houston; Icahn School of Medicine at Mount Sinai; SUGEN, Inc.; University of California, San Diego; and the Howard Hughes Medical Institute before joining the faculty of the University of Missouri–St. Louis in 2004.
Yaroslava G. Yingling, PhD, is a Professor of Materials Science and Engineering at North Carolina State University. She received her University Diploma in Computer Science and Engineering from the St. Petersburg State Polytechnic University of Russia and her PhD in Materials Engineering and High Performance Computing from The Pennsylvania State University in 2002. She carried out postdoctoral research at The Pennsylvania State University Chemistry Department and at the National Institutes of Health’s National Cancer Institute prior to joining North Carolina State University in 2007. She received the National Science Foundation CAREER award, American Chemical Society OpenEye Young Investigator Award, and was named a North Carolina State University Faculty Scholar. Research interests in Professor Yingling’s group are focused on the development of soft materials informatics tools, advanced computational models, and algorithms for multi-scale molecular modeling of soft and biological materials, and aim to provide a fundamental understanding of the structure–property relations of a variety of soft materials systems that are formed through the process of self-assembly.
BOARD ON LIFE SCIENCES, BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY, AND THE NATIONAL ACADEMIES
BOARD ON LIFE SCIENCES
JAMES P. COLLINS, Arizona State University
A. ALONSO AGUIRRE, George Mason University
ENRIQUETA C. BOND, Burroughs Wellcome Fund
DOMINIQUE BROSSARD, University of Wisconsin–Madison
ROGER D. CONE, University of Michigan
NANCY D. CONNELL, Rutgers New Jersey Medical School
SEAN M. DECATUR, Kenyon College
JOSEPH R. ECKER, Salk Institute for Biological Studies
SCOTT V. EDWARDS, Harvard University
GERALD L. EPSTEIN, National Defense University
ROBERT J. FULL, University of California, Berkeley
ELIZABETH HEITMAN, Vanderbilt University Medical Center
JUDITH KIMBLE, University of Wisconsin–Madison
MARY E. MAXON, Lawrence Berkeley National Laboratory
ROBERT NEWMAN, Independent Consultant
STEPHEN J. O’BRIEN, Nova Southeastern University
CLAIRE POMEROY, Albert and Mary Lasker Foundation
MARY E. POWER, University of California, Berkeley
SUSAN RUNDELL SINGER, University of California, Berkeley
LANA SKIRBOLL, Sanofi
DAVID R. WALT, Harvard Medical School
FRANCES SHARPLES, Director
LIDA ANESTIDOU, Senior Program Officer
KATHERINE BOWMAN, Senior Program Officer
ANDREA HODGSON, Program Officer
JO HUSBANDS, Senior Scholar
KEEGAN SAWYER, Senior Program Officer
AUDREY THEVENON, Program Officer
BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY
DAVID BEM, PPG Industries
JOAN BRENNECKE, NAE, Notre Dame University
GERARD BAILLELY, Procter & Gamble Company
MARK BARTEAU, NAE, University of Michigan
MICHELLE V. BUCHANAN, Oak Ridge National Laboratory
JENNIFER SINCLAIR CURTIS, University of California, Davis
SAMUEL H. GELLMAN, NAS, University of Wisconsin–Madison
SHARON C. GLOTZER, NAS, University of Michigan
MIRIAM E. JOHN, Sandia National Laboratories (Retired)
ALAN D. PALKOWITZ, Eli Lilly and Company
JOSEPH B. POWELL, Shell
PETER J. ROSSKY, NAS, Rice University
RICHMOND SARPONG, University of California, Berkeley
LAURA DEFEO, Director (Acting)
MARILEE SHELTON-DAVENPORT, Senior Program Officer
CAMLY TRAN, Senior Program Officer
ANNA SBEREGAEVA, Associate Program Officer
JESSICA WOLFMAN, Senior Program Assistant
JARRETT NGUYEN, Senior Program Assistant
SUZANNE THILENIUS, Administrative Coordinator
NICHOLAS ROGERS, Financial Associate
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.
The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president.
The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.
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Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.
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This Consensus Study Report was reviewed in draft form by an individual chosen for his diverse perspective and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individual for his review of this report:
Christopher Rowley, Memorial University
Although the reviewer listed above provided many constructive comments and suggestions, he was not asked to endorse the conclusions or recommendations of this report. In addition, he was responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
The conflict-of-interest policies of the National Academies of Sciences, Engineering, and Medicine generally prohibit an individual from participating in a matter if the individual has a conflict of interest with respect to the matter.
When the committee that authored this Consensus Study Report was established, a determination of whether there was a conflict of interest with respect to any of the proposals to be reviewed by the committee was made for each committee member given the individual’s circumstances and the task being undertaken by the committee. A determination that an individual has a conflict of interest is not an assessment of that individual’s actual behavior or character or ability to act objectively despite the conflicting interest.
The following members of the committee were determined to have a conflict of interest with respect to one or more of the proposals to be reviewed by the committee because of the nature of their relationship with the lead investigator or another member of the research team that submitted the proposal. These committee members were recused from any involvement in the review of the proposals with respect to which they had a conflict.
|Proposal Number||Committee Member(s) Recused|
|18003P||Alan Grossfield, Chung Wong|
|18014P||Yaroslava G. Yingling|
|18029P||James C. Gumbart|
|18030P||Eric May, Sadasivan Shankar|
|18035P||Nathan Baker, Yaroslava G. Yingling|
|18040P||James C. Gumbart, Yinglong Miao|
|18051P||Andrew Ferguson, James C. Gumbart, Fatemeh Khalili-Araghi|
|18069P||Andrew Ferguson, James C. Gumbart, Fatemeh Khalili-Araghi|
|18075P||James C. Gumbart, Fatemeh Khalili-Araghi|
|18076P||Andrew Ferguson, James C. Gumbart, Fatemeh Khalili-Araghi|