Report of the Committee on Proposal
Evaluation for Allocation of Supercomputing
Time for the Study of Molecular Dynamics,
Tenth Round

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

Board on Life Sciences

Division on Earth and Life Studies

A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

• 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 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 time 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 22 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 September 13, 2019. 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 79 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 51 proposals, 26 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:

CHE120043P Gregory A. Voth, The University of Chicago; Molecular Mechanisms in HIV-1 Membrane Targeting and Capsid Inhibition [Returning user identified for 230,000 MDUs]*

CHE190029P Adrian Roitberg, University of Florida; Understanding Allosteric Regulation in Human Ribonucleotide Reductase Through Computational Studies [New user identified for 412,825 MDUs]

CHE190031P Peter Kekenes-Huskey, University of Kentucky, All Campuses; Deciphering the ATP Mediated Activation of P2X4 Receptor Channels [New user identified for 460,000 MDUs]

IBN130013P Maria Bykhovskaia, Wayne State University; Protein Machinery Regulating Synaptic Vesicle Fusion [Returning user identified for 230,000 MDUs]*

MCB100017P Emad Tajkhorshid, University of Illinois at Urbana-Champaign; Biomechanics of P-Glycoprotein in Blood–Brain Barrier [Returning user identified for 360,000 MDUs]*

MCB100018P Benoit Roux, The University of Chicago; Binding Specificity of Inhibitors and Conformational Dynamics in Abl- and Src-Kinases [Returning user identified for 345,000 MDUs]*

MCB100024P Martin Gruebele, University of Illinois at Urbana-Champaign; In-Cell Structure, Binding, and Diffusion of a Fluorescent Protein Construct [Returning user identified for 460,000 MDUs]

MCB110005P Douglas James Tobias, University of California, Irvine; Atomistic Modeling of Water Permeation in Aquaporin 0 [Returning user identified for 442,661 MDUs]

MCB110012P Jeffery B. Klauda, University of Maryland, College Park; Modeling the Intracellular and Transmembrane Structure of the Active Dimer of PlexinA1 [Returning user identified for 460,000 MDUs]

MCB110023P Matthias Buck, Case Western Reserve University; Computational Modeling of Ras: Effector Protein Complex at the Membrane with Signaling Lipids PIP2 [Returning user identified for 230,632 MDUs]

MCB110059P Wonpil Im, Lehigh University; Exploration of Heat and Lipid Sensing in TRPV2 [Returning user identified for 460,000 MDUs]

MCB110066P Edward Lyman, University of Delaware; How Do Lipids Modulate GPCR Activity?: A Comparison of A1 and A2A Adenosine Receptor Activation [Returning user identified for 449,896 MDUs]

MCB120079P Rommie Amaro, University of California, San Diego; Investigating Full-Length P53 Tetramer Dynamics and Druggability by Ensemble-Based Approaches [Returning user identified for 230,000 MDUs]*

MCB120085P Maria Kurnikova, Carnegie Mellon University; Non-equilibrium Simulations of an Allosteric Gating Mechanism in Ionotropic Glutamate Receptors [Returning user identified for 153,000 MDUs]*

MCB130043P Harel Weinstein, Cornell University, All Campuses; Functional Mechanisms of Mammalian TMEM16 Phospholipid Scramblases [Returning user identified for 460,000 MDUs]

MCB130045P Albert Lau, Johns Hopkins University; Ligand-Binding Mechanisms in the NMDA Receptor [Returning user identified for 460,000 MDUs]

MCB130048P David Cowburn, Yeshiva University; FG Repeats Domain Interactions of the Nuclear Pore by Simulation and Experiment [Returning user identified for 460,000 MDUs]

MCB130061P Eduardo Perozo, The University of Chicago; C-type Inactivation in a Voltage-Gated Potassium Channel [Returning user identified for 460,000 MDUs]

MCB140052P Richard W. Pastor, National Institutes of Health; PIP2 Clustering as a Modulator of TREK-1 Activity: Reconciling Two Theories of General Anesthesia [Returning user identified for 459,400 MDUs]

MCB140056P Ron Dror, Stanford University; Rational Design of Optogenetics Tools with Desired Kinetics and Ion Selectivity [Returning user identified for 307,000 MDUs]*

MCB140062P Vladimir Yarov-Yarovoy, University of California, Davis; Multi-microsecond Simulations of Voltage-Gated Sodium Channel Function and Modulation [Returning user identified for 370,000 MDUs]*

MCB140063P 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]*

MCB150026P Diwakar Shukla, University of Illinois at Urbana-Champaign; Understanding Regulation of Rubisco Activase for Improving Photosynthetic Efficiency in Plants [Returning user identified for 306,000 MDUs]*

MCB160079P Sharon Loverde, City University of New York; Sequence Dependent Barriers to Nucleosome Unwrapping [Returning user identified for 392,170 MDUs]

MCB160080P Michael Feig, Michigan State University; Protein Crowding Near Membranes with Embedded Proteins [Returning user identified for 460,000 MDUs]

MCB160087P Mahmoud Moradi, University of Arkansas; Activation Process of Class C G—Protein Coupled Receptors [Returning user identified for 306,666 MDUs]*

MCB160089P Igor Vorobyov, University of Southern California; Molecular Determinants of Multi-Target Binding of hERG Blocking Drugs [Returning user identified for 460,000 MDUs]

MCB170088P Alexander Sobolevsky, Columbia University; Structure and Dynamics of AMPA Receptor Interactions with Auxiliary Proteins [Returning user identified for 230,000 MDUs]*

MCB170096P Baron Chanda, University of Wisconsin–Madison; Activation and Opening of Non-Domain-Swapped Voltage-Gated Channels: Applications to EAG [Returning user identified for 460,000 MDUs]

MCB170100P Janice Robertson, Washington University; Identifying the Physical Driving Forces for CLC Dimerization in Lipid Bilayers [Returning user identified for 250,000 MDUs]*

MCB180081P Liqun Zhang, Tennessee Technological University; Anton Simulation on Human Beta Defensins Binding with and Disruption Inside Lipid Membranes [Returning user identified for 230,000 MDUs]*

MCB180086P Gaurav Arya, Duke University; Mechanisms of DNA Translocation by Pentameric Viral DNA Packaging Motors [Returning user identified for 111,000 MDUs]*

MCB180087P Eric Deeds, University of Kansas, All Campuses; Understanding the Separation of Time Scales in Proteasome Assembly [Returning user identified for 230,000 MDUs]

MCB180091P William Goddard, California Institute of Technology; Structures and Mechanism for G-Protein and Beta-arrestin Signaling of GPCRs Through MD Simulations [Returning user identified for 230,000 MDUs]*

MCB190041P Krzystof Kuczera, University of Kansas, All Campuses; Dynamics and Ligand Interaction of Membrane Bound Integrin Alphavbeta3 [New user identified for 120,000 MDUs]*

MCB190044P Yun Luo, Western University; Opening the Mechanosensitive Piezo1 Channel [Returning user identified for 300,000 MDUs]*

MCB190052P Jianhan Chen, University of Massachusetts Amherst; Gating of Calcium-Activated TMEM16F and BK Channels [New user identified for 230,000 MDUs]*

MCB190053P Peter Larsson, Miller School of Medicine, University of Miami; Lipophilic Modulation of Cardiac Channel Activity as an Anti-Arrhythmic Therapy [New user identified for 230,000 MDUs]*

MCB190055P Deborah Evans, University of New Mexico, All Campuses; All-Atom Molecular Dynamics (MD) Simulations to Elucidate Amyloid-Β (Aβ) Aggregation and Aβ Interactions with Membranes in the Cellular Environment [Returning user identified for 186,000 MDUs]*

MCB190056P Wei Huang, Case Western Reserve University; Assembling Pathways of Protein Phosphatase 2A Holoenzyme Complexes with Atomic Resolution [New user identified for 110,000 MDUs]

MCB190057P Jose Faraldo-Gomez, National Institutes of Health; Mechanisms of Recognition, Selectivity and Self-Diffusion of a Human DHHC Membrane-Integral Enzyme [New user identified for 460,000 MDUs]

MCB190060P James Kindt, Emory University; Dynamics of Hemagglutinin Mediated Membrane Fusion: Simulation of Fusion Peptide Insertion and Interaction with Transmembrane Domain [New user identified for 225,000 MDUs]*

MCB190063P James Berger, Johns Hopkins Medical Institutions; ATP-Dependent Allosteric Coordination in Type IIA Topoisomerases [New user identified for 460,000 MDUs]

MCB190068P Tongye Shen, The University of Tennessee, Knoxville; Long-time Simulation of Nuclear Hormone Receptor: DNA Binding Modulates Protein Domain Interactions [New user identified for 140,000 MDUs]

MCB190070P Alexey Ladokhin, University of Kansas, All Campuses; Atomistic Modeling of Membrane-Induced Conformational Changes in Anti-Apoptotic Bcl-xL [New user identified for 230,000 MDUs]*

MCB190073P Jodi Hadden, University of Delaware; Deriving an All-Atom Model for the Full Length Hepatitis B Capsid (Cp183) [New user identified for 230,000 MDUs]*

MCB190074P Aleksei Aksimentiev, University of Illinois at Urbana-Champaign; Molecular Mechanisms of Protein–RNA Recognition in a Biological Condensate [Returning user identified for 447,911 MDUs]

MCB190076P Alexander Sodt, National Institutes of Health; Modeling Complex Lipid Effects at a Caveolar Neck to Uncover the Physics of Curved Membrane Structures [New user identified for 230,000 MDUs]*

MCB190081P Patricia Reggio, University of North Carolina at Greensboro; Endocannabinoid Interaction with the Ionotropic Cannabinoid Receptor, TRPV1 [New user identified for 417,033 MDUs]

MCB190084P Marcos Sotomayor, The Ohio State University, All Campuses; In-Silico Electrophysiology of the Inner-Ear Hair-Cell Mechanotransduction Channel TMC1 [New user identified for 460,000 MDUs]

MCB190085P David Minh, Illinois Institute of Technology; The Redox-Coupled Conformational Mechanism of Na⁺-NQR [New user identified for 115,000 MDUs]*

The time allocations for the 51 proposals identified by the committee as best meeting the selection criteria for time allocations total approximately 15,800,000 MDUs. Approximately 27.6% MDUs were allocated to proposals whose principal investigators have not received time on Anton (identified as “new users”). Approximately 72.4% 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 32,087,810 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 2019 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,

James Briggs

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

cc: Dr. Philip Blood, Pittsburgh Supercomputing Center
Dr. Gregory Symmes, National Academies of Sciences, Engineering, and Medicine
Dr. Frances Sharples, National Academies of Sciences, Engineering, and Medicine

APPENDICES

A. Table 1: Proposals Reviewed by the Committee*

B. Individual Proposal Summary Evaluations*

C. Proposal Evaluation Criteria

D. Roster and Biographical Sketches of Committee Members

E. Board on Life Sciences and the National Academies of Sciences, Engineering, and Medicine

F. Acknowledgment of Report Reviewer

G. Disclosure of Conflicts of Interest

*These appendices are not available to the public.

APPENDIX C

PROPOSAL EVALUATION CRITERIA

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:

1. Potential to advance understanding of an important problem or question in the field
2. Potential for breakthrough science resulting in new discoveries and understanding
3. Impact that successful completion of the proposed research would have on the knowledge, methods, and current barriers in the field
4. Project is scientifically and technologically feasible with clear, well-developed, and appropriate goals, objectives, and approaches to the proposed studies; a plan for analyzing the data was presented or indicated via specific publication

Justification for requested time allocation. This should be evaluated by considering:

1. Clear and well-justified need for time on Anton rather than conventional supercomputers
2. 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:

1. Appropriate experience and training to successfully conduct the proposed studies
2. Evidence of knowledge and prior experience with molecular simulations (indicated by inclusion of biosketch/CV for each of the key personnel listed and an explanation of their role in the proposed plan)
3. Past publications and demonstrated progress from previous Anton allocations or satisfactory explanation of past un-used allocation time

APPENDIX D

ROSTER AND BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS

COMMITTEE ON PROPOSAL EVALUATION FOR ALLOCATION OF SUPERCOMPUTING TIME FOR THE STUDY OF MOLECULAR DYNAMICS, TENTH ROUND

Chair

JAMES BRIGGS, University of Houston

Members

JEROME BAUDRY, The University of Alabama in Huntsville

HEATHER CARLSON, University of Michigan

LINDA COLUMBUS, University of Virginia

BRIAN DOMINY, Clemson University

JAMES C. (JC) GUMBART, Georgia Institute of Technology

ELLINOR HAGLUND, University of Hawaii at Manoa

FATEMEH KHALILI-ARAGHI, University of Illinois at Chicago

ANDRZEJ KLOCZKOWSKI, Nationwide Children’s Hospital

THEMIS LAZARIDIS, City College of New York

ERIC MAY, University of Connecticut

CLARE MCCABE, Vanderbilt University

YINGLONG MIAO, The University of Kansas

VIVEK NARSIMHAN, Purdue University

STEVEN W. RICK, The University of New Orleans

CHRISTOPHER ROWLEY, Memorial University of Newfoundland

LEONOR SAIZ, University of California, Davis

MARKUS SEELIGER, State University of New York at Stony Brook

JEFFREY SKOLNICK, Georgia Institute of Technology

JUAN M. VANEGAS, University of Vermont

TROY WYMORE, University of Michigan

YAROSLAVA G. YINGLING, North Carolina State University

Project Staff

STEVEN MOSS, Project Director, Board on Life Sciences

ANDREA HODGSON, Program Officer, Board on Life Sciences

JESSICA DE MOUY, Senior Program Assistant, Board on Life Sciences

BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS

Chair

James Briggs, Ph.D., is a Professor within the Biology and Biochemistry Department at the University of Houston. Dr. Briggs received his Ph.D. 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 areas. Targets for these studies include those important in the treatment of AIDS, cancer, bacterial infections, and other disease states. In addition, Dr. Briggs has worked on inhibitors to aid in biowarfare defense (botulinum neurotoxins, anthrax toxin, cholera toxin). Dr. Briggs’s research is focused in the highly interdisciplinary and collaborative area of computational chemistry and 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 and discovery and computational biophysics. His main target areas in the inhibitor and 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 enzyme function from structure only.

Members

Jerome Baudry, Ph.D., is the Pei-Ling Chan Professor of Biological Sciences in the Department of Biological Sciences at The University of Alabama in Huntsville (UAH). Dr. Baudry obtained his Ph.D. in Molecular Biophysics from the University of Paris and the Pierre and Marie Curie University/Sorbonne University in 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, Knoxville (UT), 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 of Biological Sciences. 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.

Heather Carlson, Ph.D., is currently a Professor of Medicinal Chemistry in the College of Pharmacy at the University of Michigan. She also holds joint appointments with the Biophysics Department and the Chemistry Department in the College of Literature, Science, and the Arts. Dr. Carlson received both her master’s degree and Ph.D. in Physical Chemistry from Yale University, and completed her postdoctoral work at the University of California, San Diego. Her expertise is in the area of computer simulations, cheminformatics, bioinformatics, and structure-based drug design. She is a leader in the incorporation of protein flexibility and allosteric control in drug design. She is also well known for her studies of protein-ligand binding and the biophysics of molecular recognition. Dr. Carlson is also the director of two large, online resources for studying protein-ligand interactions: Binding MOAD (Mother of All Databases) (www.bindingmoad.org) and the Community Structure-Activity Resource (www.csardock.org). These resources are used by numerous research groups around the world. She also serves the scientific community through National Institutes of Health review panels and editorial roles for scientific journals.

Linda Columbus, Ph.D., is a Professor of Chemistry at the University of Virginia. Dr. Columbus received her bachelor’s degree in Chemistry from Smith College and her Ph.D. in Biochemistry and Molecular Biology from the University of California, Los Angeles. Dr. Columbus’s lab focuses on using biophysical chemistry to study membrane biophysics and membrane protein structure, function, and dynamics. Her

research specifically looks at the structure and dynamics of membrane proteins involved in bacterial pathogenesis. To facilitate this research, her lab develops and uses approaches such as site-directed spin labeling, nuclear magnetic resonance spectroscopy, and X-ray crystallography.

Brian Dominy, Ph.D., is an Associate Professor in the Department of Chemistry at Clemson University. Dr. Dominy earned his B.S. from Carnegie Mellon University in the Biological Sciences and Computer Science tracks with a minor in Chemistry. He then joined the Scripps Research Institute as a Ralph M. Parsons Foundation predoctoral fellow, earning his Ph.D. under the direction of Dr. Charles L. Brooks III. Following this, he worked as a National Institutes of Health postdoctoral fellow at Harvard University with Dr. Eugene Shakhnovich in the Department of Chemistry and Chemical Biology. During this time, his research dealt with improving statistical mechanical models, primarily inverse Boltzmann knowledge-based potentials, designed for rapid binding free energy prediction and automated drug design. His current research involves the development and application of molecular mechanics and bioinformatics techniques to explore the physical chemical basis of biological phenomena at the molecular level. Specifically, his group focuses on applications relevant to medicine, including drug design and the biomolecular evolution of drug targets (i.e., drug resistance).

James C. (JC) Gumbart, Ph.D., is an Associate Professor of Physics at the Georgia Institute of Technology in Atlanta, Georgia. He obtained his B.S. from Western Illinois University and his Ph.D. in Physics from the University of Illinois at Urbana-Champaign 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.

Ellinor Haglund, Ph.D., is currently an Assistant Professor in the Department of Chemistry at the University of Hawaii at Manoa. Dr. Haglund received her master’s degree in Molecular Biology and Chemistry from Umeå University, her Ph.D. at Stockholm University, and completed her postdoctoral work at Rice University and the University of California, San Diego, with the Center for Theoretical Biological Physics. Her research is focused on the folding event in proteins, utilizing both computational and experimental techniques to understand the molecular details of how proteins fold into biologically active molecules. She is inspired by how nature works and utilizes her multidisciplinary training to answer questions at the interface of chemistry, biology, and physics.

Fatemeh Khalili-Araghi, Ph.D., is an Assistant Professor at the University of Illinois at Chicago, specializing in theoretical and computational studies of ion channels. She obtained her B.S. in Physics from Sharif University of Technology and her Ph.D. from the University of Illinois at Urbana-Champaign. She was a postdoctoral scholar at The University of Chicago, where she continued studies of membrane proteins with a focus on the Na/K ATPase using computational modeling techniques, as well as molecular dynamics simulations. She currently works on transport properties of tight junctions and bacterial efflux pumps.

Andrzej Kloczkowski, Ph.D., is a Principal Investigator in the Battelle Center for Mathematical Medicine of The Abigail Wexner Research Institute at Nationwide Children’s Hospital. He has a joint appointment as a Professor of Pediatrics at the College of Medicine at The Ohio State University. Dr. Kloczkowski’s research program focuses on computational structural biology and bioinformatics, including protein structure prediction from the amino acid sequence, prediction of biomacromolecular dynamics using elastic network models, the development of coarse grained models and potentials for proteins and nucleic acids, and studies of protein-protein and protein-nucleic acid integrations. He is also interested in the application of machine learning methods to various biomedical and clinical problems, and has ongoing collaboration with several experimental and clinical centers.

Themis Lazaridis, Ph.D., is currently a Professor in the Department of Chemistry and Biochemistry at the City College of New York, affiliated with the CUNY Institute for Macromolecular Assemblies. Dr. Lazaridis earned his Ph.D. in Chemical Engineering from the University of Delaware, followed by postdoctoral work at Harvard University. His research is in the area of theoretical and computational biophysical chemistry, which aims to understand how biological systems work in terms of the fundamental laws of physics and chemistry. One goal of his research is to understand the forces that operate within and between biomolecules and develop quantitative mathematical models for their energy as a function of conformation. Such models are useful in many ways, such as predicting the three-dimensional structure from sequence, characterizing conformational changes involved in biological function, or predicting the binding affinity between two biomolecules. A particular focus in the past several years has been the interaction of proteins with biological membranes and pore formation in lipid bilayers.

Eric May, Ph.D., is an Associate Professor in the Department of Molecular and Cell Biology at the University of Connecticut. He obtained his Ph.D. from the University of Florida in Chemical Engineering and was a National Science Foundation postdoctoral fellow at the University of Michigan. His research interests are in the general area of computational and theoretical biophysics and biochemistry, with emphasis toward understanding conformational and phase transitions and the mechanical and thermodynamic properties of biological materials. His research group works on a variety of biomolecular systems, with particular emphasis on virus and membrane systems and protein dynamics.

Clare McCabe, Ph.D., received her bachelor’s degree and Ph.D. 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. She is currently a faculty member at Vanderbilt University, where she is the Cornelius Vanderbilt Chair of Engineering and a Professor of Chemical and Biomolecular Engineering. Dr. McCabe 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. 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, Ph.D., 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 Ph.D. in Computational Chemistry in the lab of Peter Ortoleva at Indiana University. His graduate work was focused on all-atom multiscale 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 the 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 that are responsible for drug metabolism. Dr. Miao then moved to Andy McCammon’s lab at the Howard Hughes Medical Institute and the University of California, San Diego, where he worked on both method developments and cutting-edge applications in accelerated biomolecular simulations and drug discovery of the 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.

Vivek Narsimhan, Ph.D., is an Assistant Professor of Chemical Engineering at Purdue University. Dr. Narsimhan received his bachelor’s degree in Chemical Engineering from the California Institute of Technology, his master’s degree in Advanced Study in Mathematics from the University of Cambridge, his Ph.D. in Chemical Engineering from Stanford University, and completed his postdoctoral research at the Massachusetts Institute of Technology. His research uses a mixture of theory, simulations, and experiments to examine problems in the areas of suspensions, complex interfaces, fluid mechanics, and polymers. He

has developed mathematical models, performed simulations, and conducted experiments to describe the mechanics of droplets, red blood cells, and vesicles under various flow types and microfluidic geometries. These investigations provide insight into how complex membranes alter the mechanical stability and motion of fluid-filled particles, both individually and as a suspension.

Steven W. Rick, Ph.D., is a Professor in the Chemistry Department at the University of New Orleans. Dr. Rick received his bachelor’s degree from the University of California, Los Angeles, his Ph.D. from the University of California, Berkeley, and completed his postdoctoral research at Columbia University. His research applies theoretical and computational approaches to a variety of chemically interesting systems. His work involves the development of more efficient computer simulation methods and better models for molecular interactions. Dr. Rick’s group is applying these methods to the study of liquid water, interface, aqueous solutions, proteins, and ion transport through various materials.

Christopher Rowley, Ph.D., is an Associate Professor in the Department of Chemistry at the Memorial University of Newfoundland. Dr. Rowley’s research interests are in computational chemistry, statistical thermodynamics, medicinal chemistry, biophysical chemistry, protein folding, and multiscale modeling. His research group uses application-driven method development to investigate issues of irreversible enzyme inhibition, ion solvation, and membrane permeation. Dr. Rowley received his Ph.D. in Chemistry from the University of Ottawa.

Leonor Saiz, Ph.D., is a Professor in the Biomedical Engineering Department at the University of California, Davis. Dr. Saiz received her Ph.D. in Physics from the University of Barcelona. Her research involves the study of the dynamics of biological networks at the cellular and molecular level. Her lab combines computational and theoretical approaches together with experimental data to (1) understand how cellular behavior arises from the physical properties and interactions of the cellular components; and to (2) infer detailed molecular properties, such as the in vivo DNA mechanics, from the cellular physiology. By developing novel methodologies that consider multiple spatial and temporal scales and multiple levels of biological organization, including atomic, molecular, and cellular, the lab’s work has provided new avenues to integrate the molecular properties of cellular components directly into the dynamics of cellular networks. The ultimate goal of her work is to understand and follow the impact of molecular perturbations in the cellular components, such as a mutation in a protein or interventions with small molecules or drugs, through the different cellular processes up to the cellular behavior; one of the major challenges of modern biomedical sciences.

Markus Seeliger, Ph.D., is an Associate Professor for Pharmacological Sciences and Associate Faculty of the Laufer Center for Computational and Physical Biology at State University of New York at Stony Brook’s School of Medicine. Dr. Seeliger received his Ph.D. in Biophysical Chemistry from Cambridge University. The research in his group circles around the questions: How can we help small molecule inhibitors become clinically successful drugs? and What can we learn about the molecular regulation of drug targets through their interaction with small molecule drugs? He combines X-ray crystallography, nuclear magnetic resonance, and other biophysical methods with computational tools.

Jeffrey Skolnick, Ph.D., is a Professor, the Mary and Maisie Gibson Chair, and the GRA Eminent Scholar in Computational Systems Biology at the Georgia Institute of Technology. He received his B.A. in Chemistry from Washington University in St. Louis in 1975, his M.Phil. in Chemistry from Yale University in 1977, and his Ph.D. in Chemistry from Yale University in 1978. His research interests include using systems and computational biology approaches to solve health problems. He uses these tools to better understand important areas of study such as cancer metabolomics, drug design, and protein evolution. An additional area of research includes the prediction of protein structure from DNA sequences to better characterize human genes.

Juan M. Vanegas, Ph.D., is currently an Assistant Professor at the University of Vermont in the Department of Physics with appointments in the Materials Science and Cellular, Molecular, and Biomedical Sciences Graduate Programs. Dr. Vanegas received his master’s degree in Biochemistry and Biophysics from Oregon State University and his Ph.D. in Biophysics from the University of California, Davis. His research uses coarse-grained, atomistic, and ab initio molecular simulation methods to understand how chemical structure determines mechanical properties of biomolecules and their response to mechanical stimuli. Some applications of this research include understanding elastic properties of lipid biomembranes and force transduction mechanisms in mechanosensitive channels. His lab leads the development of computational tools for local stress calculations from molecular dynamics simulations.

Troy Wymore, Ph.D., is an Assistant Research Scientist and Lecturer in the Chemistry Department at the University of Michigan. He received his B.S. and Ph.D. in Chemistry from the University of Missouri–Columbia. His research leverages molecular phylogenetic analyses and ancestral sequence reconstruction to help frame questions and develop hypotheses directed toward understanding sequence-structure-function relationships. His lab is particularly interested in the impact that residues outside the active site have on the evolution of new enzyme functions and how this information can be leveraged to redesign enzymes for alternative purposes. To test the lab’s hypotheses, atomistic models of enzymes are constructed and often molecular dynamics simulations are performed first to understand fluctuations in the structure and ligand-binding to an allosteric or active site.

Yaroslava G. Yingling, Ph.D., 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 Saint Petersburg State Technical University of Russia and her Ph.D. in Materials Engineering and High Performance Computing from The Pennsylvania State University in 2002. She carried out postdoctoral research at the Chemistry Department at The Pennsylvania State University 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 Open Eye 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 multiscale 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.

APPENDIX E

BOARD ON LIFE SCIENCES AND THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE

BOARD ON LIFE SCIENCES

Chair

JAMES P. COLLINS, Arizona State University

Members

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, Johns Hopkins Center for Health Security

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, University of Texas Southwestern Medical Center

MARY E. MAXON, Lawrence Berkeley National Laboratory

ROBERT NEWMAN, The Aspen Institute

STEPHEN J. O’BRIEN, Nova Southeastern University

CLAIRE POMEROY, Albert and Mary Lasker Foundation

MARY E. POWER, University of California, Berkeley

SUSAN RUNDELL SINGER, Rollins College

LANA SKIRBOLL, Sanofi

DAVID R. WALT, Harvard Medical School

Staff

FRANCES SHARPLES, Director

KATHERINE BOWMAN, Senior Program Officer

JESSICA DE MOUY, Senior Program Assistant

ANDREA HODGSON, Program Officer

JO HUSBANDS, Senior Scholar

STEVEN MOSS, Associate Program Officer

KEEGAN SAWYER, Senior Program Officer

AUDREY THEVENON, Program Officer

KOSSANA YOUNG, Senior Program Assistant

APPENDIX F

ACKNOWLEDGMENT OF REPORT REVIEWER

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:

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.

APPENDIX G

DISCLOSURE OF CONFLICTS OF INTEREST

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 principal 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.