APPENDIX D

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

Chair

ROBERT EISENBERG, Rush University

Members

JAMES BRIGGS, University of Houston

KAREN FLEMING, Johns Hopkins University

ANGEL GARCIA, Los Alamos National Laboratory

DONALD HAMELBERG, Georgia State University

FATEMEH KHALILI-ARAGHI, University of Illinois at Chicago

GLENN MARTYNA, IBM T.J. Watson Research Center

CLARE MCCABE, Vanderbilt University

BLAKE MERTZ, West Virginia University

SERGEI NOSKOV, University of Calgary

CHRISTOPHER ROWLEY, Memorial University

DAVID SEPT, University of Michigan

SADASIVAN (SADAS) SHANKAR, Harvard University

ERIKA TAYLOR, Wesleyan University

MARK TUCKERMAN, New York University

FENG WANG, University of Arkansas

CHUNG WONG, University of Missouri

YINGHAO WU, Albert Einstein College of Medicine

TROY W. WYMORE, University of Michigan

Project Staff

KEEGAN SAWYER, Project Director, Board on Life Sciences

LAURA DEFEO, Director, Program & Policy

ANNA SBEREGAEVA, Associate Program Officer, Board on Chemical Sciences and Technology

ANGELA KOLESNIKOVA, Sr. Program Assistant, Board on Life Sciences

BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS

Chair

Robert Eisenberg is the Bard Endowed Professor and Chairman emeritus, Department of Molecular Biophysics & Physiology, Rush University. Eisenberg has been working at the interface of physics, physiology, and computation since he used Green's functions to solve and compute the linear electrical properties of nerve cells and has worked on multiple scales, from inside ion channels, to cell membranes, cells, and tissues. All of this work has used computation to allow theories to confront real experimental data taken on physiological scales. Eisenberg’s recent work has concentrated on understanding the selectivity of calcium (e.g., L-type cardiac) and sodium channels, an area in which he has done extensive (about 30 papers) Monte Carlo simulations and a wide variety of multi-scale models. Dr. Eisenberg can bring to the Advisory Board a) knowledge of what needs to be computed to be useful for understanding natural function (e.g., the role of TRACE concentrations of calcium and messengers which are exceedingly difficult to simulate because of the immense number of water molecules needed to dilute the calcium and messenger ions); b) an appreciation of the necessity of calibration (validation and verification) in simulations as in experiments. In experiments, if things are not checked continually, results often have limited utility; and c) knowledge of the role of the electric field from tissues, to cells, to ions, and the various multi-scale treatments needed to meld with atomic scale simulations, so the simulations can reach biological length and time scales.

Members

James Briggs Ph.D., is an Associate 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 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 neurotoxins, anthrax toxin, cholera toxin).

Karen Fleming is a tenured professor in T.C. Jenkins Department of Biophysics at Johns Hopkins University. Her research is motivated by the power a deep understanding of the physics/biology intersection can bring to disease, evolution and biological design. Her approaches are driven by the unique powers that biophysics can bring to solving complex cellular problems. For many years, Dr. Fleming studied the energetics of transmembrane helix-helix interactions. She has developed theory to describe their associations; defined conditions of “forced cohabitation” of helices in micelles and has discovered thermodynamic coupling in helix-helix dimerization reactions. Recently Dr. Fleming’s work has targeted the protein-folding problem using transmembrane β-barrels. Her lab managed to quadruple the number of known membrane protein stabilities; we developed a novel water-to-bilayer side chain hydrophobicity scale and showed that aromatic side chain energies follow the polarity gradient inherent in a phospholipid bilayer. She received her B.A. in French and Pre-Medical Studies at the University of Notre Dame and her Ph.D. in Biochemistry and Molecular Biology from Georgetown University.

Angel Garcia is currently the Director of the Center for Nonlinear Studies at Los Alamos National Laboratory. Previously he was Department Head of the Physics, Applied Physics and Astronomy Department at Rensselaer Polytechnic Institute. He was also Professor of Physics and Senior Constellation Chaired Professor of Biocomputation and Bioinformatics. The Garcia Research Group focuses on the use of theoretical and computational methods to study aspects related to biomolecular dynamics and statistical mechanics. Their main research objectives are to understand the folding,

dynamics and stability of biomolecules. Research interests include the hydrophobic effect, enzyme catalysis, nucleic acid structure and dynamics, RNA folding, electrostatics, protein hydration, and peptide interactions with membranes. Dr. García received a Ph.D. 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 AAAS, 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, Molecular Simulations, and a member of the Faculty of 1000 for BioMed Central.

Donald Hamelberg is an Associate Professor in the Department of Chemistry at Georgia State University. Dr. Halmelberg’s research focuses on he application and development of theoretical and computational methods with the intent of gaining an in-depth understanding of biological interactions and functions. In these endeavors, Dr. Hamelberg’s laboratory uses simulation based approaches, related statistical mechanics, and classical and quantum mechanical methods. He also studies advanced simulation methods to study the dynamic fluctuations of biomolecules, as well as the hydration effects at binding sites and interfaces in biomolecular interactions.

Fatemeh Khalili-Araghi specializes in theoretical and computational studies of ion channels at the University of Illinois at Chicago as an Assistant Professor. She obtained her B.S. in Physics from Sharif University of Technology in 2001, and her PhD from University of Illinois at Urbana-Champaign in 2010. She has been a postdoctoral scholar at the University of Chicago from 2010 to 2013, where she has 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 on theoretical and computational studies of membrane proteins.

Glenn Martyna received his Ph.D. from the Columbia University and subsequently became a NSF Postdoctoral Fellow in Computational Science and Engineering at the University of Pennsylvania. He was a tenured faculty member at Indiana University, Bloomington before joining IBM Research and was later named an Honorary Professor of Physics at The University of Edinburgh, UK. Dr. Martyna’s research is focused on the atomistic modeling of soft condensed matter and materials systems as well as novel device physics, in addition to his interest in physics based computational methodology development. He is currently working to combine physical measurements with theory to study antimicrobial peptides and developing a new post-CMOS technology based on strain transductions that promises low power and high speed. He has co-authored approximately 125 papers, several of which are citations classics - papers with more than 1000 citations. Dr. Martyna has 12,000 citations total and a hindex>40.

Clare McCabe received her B.Sc. in Chemistry in 1995 and Ph.D. in 1999 from Sheffield University. Her PhD. was under the direction of George Jackson (now at Imperial College, UK) and focused on the statistical mechanics of chain molecules using the statistical associating fluid theory (SAFT) approach. After postdoctoral (1999-2000) and research faculty (2000-2001) 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 August of 2004 she moved to Vanderbilt University where she is now an Associate Professor of Chemical and Biomolecular Engineering and (since 2008) of Chemistry. McCabe has published over 100 papers in refereed journals and is a fellow of the Royal Society of Chemistry. Her research interests focus on the use of molecular modeling techniques, including molecular simulation, computational quantum chemistry and molecular-based equations of state, to understand and predict the thermodynamic and transport properties of chemical and biological systems.

Blake Mertz is an Assistant Professor in the Department of Chemistry at West Virginia University. Dr. Mertz’s research focuses on using computational biophysics and experimental methods to investigate the structure-function relationships of membrane proteins, with an emphasis on the design of membrane

scaffolds for bacterial proton pumps; characterization and design of membrane insertion peptides; drug development; and optimization of bioelectronic circuits. The underlying theme of his research is to provide more detailed understanding and predictive capabilities of systems of interest to researchers in both medicine and alternative energy. Dr. Mertz received his PhD in Chemical Engineering from Iowa State University.

Sergei Noskov is an Associate Professor at the Institute of Biocomplexity and Informatics at the University of Calgary. His research interests include molecular modeling, membrane proteins (ion channels and ion-coupled transporters), quantum chemistry of biologically relevant molecules, free energy profiles, and protein structure/function prediction. Dr. Noskov’s lab is comprised of a group of theoretical biologists and chemists interested in the understanding of molecular determinants of ligand transport across cellular membranes. Projects in his lab focus on studies of the family of fundamentally important ion-coupled neurotransmitter transporters implicated in diverse mechanisms of signal transduction in the brain. The studies of Dr. Noskov and his team resulted in a series of methods and software developed in close collaboration with other theoretical groups across the world. Dr. Noskov received his Ph.D. from the Russian Academy of Sciences and completed his postdoctoral studies within the Department of Biochemistry and Structural Biology at Weill Medical College of Cornell University. In Canada, Dr. Noskov is a recipient of the AHFMR Scholar, CIHR New Investigator, and AIF New Faculty awards. In the European Union, he is the recipient of the INTAS Young Scientist Award. Finally, in the U.S., he is the recipient of the Academia Sinica Research Fellowship and the American Epilepsy Foundation Post-Doctoral Fellowship awards.

Christopher Rowley is an Assistant 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 multi-scale modeling. His research group uses application-driven method development to investigate issues irreversible enzyme inhibition, ion solvation, and environmental pollutants. Dr. Rowley received his Ph.D in Chemistry from the University of Ottawa.

David Sept is a Professor of Biomedical Engineering at the University of Michigan in Ann Arbor. Research in the Sept lab covers four primary areas. The first focus is on the molecular interactions underlying cell migration, a process central to many aspects of development, differentiation and the cellular response to diseases such as cancer. The second focus is work characterizing and developing drugs that target sub-cellular filaments to treat parasitic diseases like toxoplasmosis, leishmaniasis and malaria. The third area of research concerns channels that regulate the flow of ions in and out of the cell, how these channels are activated and how they malfunction in diseases such as epilepsy. The final research area is on nanoparticle based drug delivery and how these particle drug combinations are metabolized and distributed within the body.

Sadasivan (Sadas) Shankar Ph.D., is the first Margaret and Will Hearst Visiting Lecturer in Computational Science and Engineering at Harvard School of Engineering and Applied Sciences. In fall 2013, as the first Distinguished Scientist in Residence at the Institute of Applied Computational Sciences in 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. Sadasivan earned his Ph.D. in Chemical Engineering and Materials Science from University of Minnesota, Minneapolis. Sadasivan 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: 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 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 still kills more than 500,000 people in the world each year. As a faculty member at Wesleyan, 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-bourne illnesses including E. coli, Salmonella, and V. cholerae); and (2) could improve the efficiency of biomass to biofuel conversion, in particular the breakdown and bacterial utilization of lignin. Erika earned an honors Chemistry undergraduate degree from the University of Michigan and her Ph.D. 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.

Mark Tuckerman is professor of Chemistry at New York University. He earned his B.S. in Chemistry from the University of California at Berkeley and his Ph.D. from Columbia University. He served as a postdoctoral fellow at IBM Forschungs-laboratorium in Zurich, Switzerland. Dr. Tuckerman’s research includes Modern theoretical methods combined with advanced scientific computing has transformed the ability to perform modeling and simulation studies of key processes in chemistry, nanoscience, and biology that generate realistic results with full atomic resolution. The research efforts in his group are focused on advancing this emerging capability and applying it to chemically important problems. Currently, Dr. Tuckerman and his team are investigating how protons are transported through various hydrogen-bonded media (water, liquid and solid acids, acid hydrates, and doped salt crystals) with an eye toward understanding and designing materials for proton-exchange membranes in fuel cells. These studies employ the method of ab initio molecular dynamics, in which the finite-temperature dynamics of a system is generated via electronic structure calculations performed “on the fly”. Using this approach, they are also studying how organic molecules attach to semiconducting surfaces, and are developing new approaches for conformational sampling in complex systems such as biomolecules and crystalline polymorphs.

Feng Wang received his B.S. in Chemistry from Peking University (1998) and Ph.D. in Theoretical Chemistry from the University of Pittsburgh (2003) with Professor Kenneth D. Jordan. He did postdoctoral research in computational physical chemistry at the University of Utah with Professor Gregory A. Voth. He was an Assistant Professor in the Department of Chemistry at Boston University from 2005 to 2012. He currently holds an associate professor position in the department of chemistry and biochemistry at University of Arkansas. While at the University of Pittsburgh, Dr. Wang received an IBM graduate student award in 2001 and a Mellon Fellowship in 2002. He received a NSF CAREER Award in 2007 and an HP outstanding Junior Faculty Award in 2010. His research focuses on developing high quality force fields, free energy calculations, and enhanced sampling.

Chung Wong Ph.D., is a Professor within the Department of Chemistry and Biochemistry at the University of Missouri-St. Louis. He received his B.Sc. (Hons.) degree from the Chinese University of Hong Kong and his Ph.D. 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, Mount Sinai School of Medicine, SUGEN, Inc., University of California-San Diego, and the Howard Hughes Medical Institute before joining the faculty of University of Missouri-St. Louis in 2004.

Yinghao Wu is an Assistant Professor in the Department of Systems & Computational biology at Albert Einstein College of Medicine. By integrating computational analysis with experimental measurements, Dr. Wu’s research focuses on developing multi-scale modeling frameworks to study the cross-talks between cell adhesion and cell signaling. He is particularly interested in why and how different cells form contacts, when and where these contacts are formed at specific locations of the human body, the functional impacts to the downstream signaling, and to human health.

Troy W. Wymore is an Assistant Research Scientist at the University of Michigan. He received his B.S. and PhD in Chemistry from the University of Missouri-Columbia. His current research focuses on applying hybrid QC/MM simulations to investigate the enzymatic mechanisms of DFPase, Xylose Isomerase, and 5-epi-aristolocholene synthase. The results of these studies provide insight into strategies for redesigning these enzymes to more effectively degrade nerve agents (DFPase) and improve the process of biofuel and pharmaceutical agent production.