Curriculum vitae
Summary
Experienced academic researcher in computational chemistry, physics, engineering and biology; proficient in theory and method development, scientific software development, with a track record of successful research grant proposals, collaboration with theoretical, computational and experimental groups, and supervision of students.
Education
2008- Research fellow with Prof. Martin Karplus, Harvard University
2006-08 Postdoctoral trainee with Prof. Bernhardt Trout, MIT
2006 Ph.D., Mechanical Engineering, University of Maryland, College Park Dissertation advisor: Prof. Ugo Piomelli
2004 M.S., Mechanical Engineering, University of Maryland, College Park (GPA 4.0)
2001 B.S.(summa cum laude), Biochemistry, Mathematics, Georgetown University, Washington DC
Research Interests
• Theoretical modeling in immunology
• Computational vaccine design
• Atomistic free energy and entropy simulation methods for biological systems
• Protein-ligand binding simulation methods
• Molecular simulation of conformational transitions in proteins
• Calculation of reaction rates in complex biomolecular processes
• Simulations of lipid membranes
• Development of molecular mechanics force fields
• Hybrid continuum/particle-based simulation methods
• Simulations of fluid/structure interaction
• Simulation of laminar turbulent and transitional flows
• Numerical methods for elliptic PDEs
• Scientific computing with Graphical Processors (GPUs)
• High-Performance Scientific Computing (HPSC) in Unix/Linux with Fortran77-2008, C/C.5ex++, Python, Matlab
• Code development for popular molecular simulation software CHARMM, NAMD2, OPENMM, ACEMD
• Small HPSC cluster design, assembly, maintenance
Research Support
2008-2010 Ruth L. Kirschstein NIH Individual National Research Service Award (1F32GM083422-01) Title: Myosin VI steps backwards: a computational study to elucidate the mechanism
2014-2016 R03 (5R03AI111416-01) Title: Modeling atomic structure of the EmrE multidrug pump to design inhibitor peptides (Co-PI with M. Karplus)
2019-present Bill and Melinda Gates Foundation grant opportunity OPP1214161 Title: Toward a permanent influenza vaccine: design of hemagglutinin antigen analogs and vaccination protocols by structural modeling, atom-based simulations, machine learning, and experiments (Co-PI with M. Karplus)
Selected Research Experience
Harvard University, Dept. of Chemistry and Chemical Biology, Cambridge, MA: 2008-present
2019-present: Design of influenza immunogens for a universal and permanent flu vaccine Co-directed and co-implemented research in the group to engineer, using various computational methods, immunogens for vaccination (currently in experimental testing); developed theoretical and computer models of affinity maturation in immunology to guide the development of universal vaccines.
2019-20: A restrained locally enhanced sampling method (RLES) for finding free energy minima in complex systems Designed, implemented, and tested a computational method to simulate concurrently a set of weakly interacting replicas of a molecular system, permitting more efficient exploration of configurations and convergence to free energy minima.
2018-19: Microsecond molecular dynamics simulations of proteins using a quasi-equilibrium solvation shell model Developed and tested a method to simulate biomolecules such as proteins and nucleic acids using only a thin layer of solvent around the biomolecule; this leads to several-fold acceleration of simulations.
2016-17: Elicitation of broad-based antibody immunity against HIV
Developed methods to compute efficiently using GPU-accelerated molecular dynamics the absolute binding affinity between antibodies and antigens; applied method to antibody/antigen complexes relevant for HIV vaccine design.
2016-17: Development of a small-molecule inhibitor for the TRAF-6 protein
Using small-molecule force-field parametrization tools, MD and free energy simulation, designed a lead-like compound for competitive inhibition of TRAF-6 signaling protein.
2014-16: Refinement of atomic structure of EmrE transporter and design of inhibitors
Developed a method to refine Xray protein structures from electron density; applied the method to obtain an all-atom structure of the EmrE multidrug transporter in E. Coli; the structure has since been used by others to refine additional structures with different ligands.
2014-16: Absolute protein-ligand binding affinities
Developed fast new methods to compute absolute ligand-protein binding affinities using GPU-accelerated code OPENMM.
2014-16: Stability prediction of small designed proteins
Developed an GPU-accelerated enhanced MD simulation protocol using ACEMD to predict the stability of proteins designed de novo using Rosetta (collaboration with David Baker’s group).
2015-16: Simultaneous calculation of free energies and rates (e.g. , , ) for biomolecular processes
This method is being applied in the design of antibodies and EmrE inhibitors (see projects above); the method was also used to estimate the rates of conformational transitions in the cargo-binding domain of the myosin V motor.
2014-15: Coarse-grained approach to conformational change in large biomolecular assemblies using generalized network models
Extended two-conformation elastic network models to support arbitrary numbers of conformational states; this development allows to rapidly generate hypotheses regarding the dynamics of multi-protein complexes, in which each protein populates several dominant conformational states; the method was apply to the conformational dynamics of the hexameric protein recycling complex ClpX, in which each monomer was allowed to populate six coarse-grained states.
2011-14: A library of code for computing free energy and reaction rates in complex biomolecular transitions
Extended a family of transition path algorithms under the umbrella of the string method beyond proof-of-principle biological models to transitions in real proteins of biological importance, including Myosin VI and Calmodulin. Specific accomplishments include (1) the development of a parallel string code in which a large number of weakly interacting copies of a single system are treated simultaneously using hundreds to thousands of CPU cores, (2) the resolution of numerous technical challenges unique to biological systems, such as identifying appropriate coarse-grained variables, obtaining accurate transition free energy profiles, and preventing chiral inversions in amino acids, (3) and the introduction of algorithmic improvements to the finite-temperature string method, which make it a varsatile tool to study conformational transitions in proteins. Currently collaborating with other researchers who are using the string methods to understand a variety of biological and chemical problems, such as proton transfer in proteins, DNA remodeling by topoisomerases, DNA repair, and enzymatic reactions using QM/MM. The code is interfaced with several molecular dynamics simulation programs. This project won the 2014 early career award for high-impact science at the National Energy Research Supercomputing Center.
2008-10: Conformational transitions in myosin
Developed a method to study conformational transitions in the myosin VI molecular motor by all atom-molecular simulation, which allows the computational of transition paths, free energy profiles, and the corresponding reaction rates. The method was used to show demonstrate a high conformational flexibility of the ‘converter’ domain in myosin VI, which partly explain why MVI hav a very broad step size distribution compared to conventional myosins II and V.
Massachusetts Institute of Technology, Dept. of Chemical Engineering, Cambridge, MA : 2006-2008
• Studies of chemomechanical and allosteric coupling and conformational changes in the myosin V motor
Investigated conformational transitions in myosin V upon nucleotide binding using biased and targeted molecular dynamics. Showed in atomic detail how binding of ATP to myosin V in the rigor state results in the opening of the actin-binding cleft, which explains the experimentally observed ATP-induces dissociation of myosin from actin
University of Maryland, Dept. of Mechanical Engineering, College Park, MD : 2001-2006
• Graduate research with Prof. Ugo Piomelli Performed numerical simulations of turbulent and transitional wall-bounded flows using various physical models. Developed parallel finite-difference codes for the solution of the Navier-Stokes equations. Implemented turbulence models. Characterized new mechanisms of bypass transition, a process whereby laminar flow becomes turbulent more rapidly than predicted by linear stability theory. These developments are important for the design of improved airfoils.
Georgetown University, Dept. of Chemistry, Washington, DC : 1998-1999
• Undergraduate research for Prof. Paul Roepe
Developed a protocol for the purification of P-glycoprotein, which is responsible for mammalian drug resistance
• Undergraduate research in the Preventive Medicine/Biometrics Lab, USUHS, Bethesda, MD
Performed statistical analysis of biometrics data for army recruits using commercial software SPSS
Awards
• National Energy Resource Supercomputing Center (NERSC) Award for High-Impact Scientific Achievement, 2014
• National Research Service Award (NRSA) Postdoctoral Fellowship, 2008-2010
• Pi Tau Sigma Graduate Student Teaching Award, 2005
• Achievement Rewards for College Scientists (ARCS) Foundation Endowment Fellowship, 2004
• Jacob K. Goldhaber Grant, University of Maryland, 2004
• Graduate Fellowship, University of Maryland, 2002-2004
• American Institute of Chemists Outstanding Achievement Award, 2001
• Phi Beta Kappa
• Phi Kappa Phi
• Pi Mu Epsilon
Professional Duties & Service
Supervision of students
• Supervised two graduate and two undergraduate students
• Co-directed an undergraduate thesis
Teaching
• Co-author of a Responsible Conduct of Research course at Harvard University (Fall 2010)
Reviewer assignments
• PNAS
• AIP Advances
• ASME Journal of Fluids Engineering
• Biophysical Journal
• Journal of Chemical Physics
• Journal of Chemical Theory and Computation
• Journal of Fluid Mechanics
• Journal of Physical Chemistry
• PROTEINS
• Undergraduate thesis reader for Harvard College, 2021
Peer-Reviewed Publications
1. V. Ovchinnikov, A. Munasinghe, and M. Karplus. Molecular simulation of stapled peptides. In T. Simonson, editor, Computational peptidology: Methods and Protocols, Methods in Molecular Biology, in press. Springer, New York, 2021.
2. Pedro Ojeda-May, Ameeq Ui Mushtaq, Per Rogne, Apoorva Verma, Victor Ovchinnikov, Christin Grundström, Beata Dulko-Smith, Uwe H. Sauer, Magnus Wolf-Watz, and Kwangho Nam. Dynamic connection between enzymatic catalysis and collective protein motions. Biochemistry, in press, 2021.
3. V. Ovchinnikov, S. Conti, E.Y. Lau, F.C. Lightstone, and M. Karplus. Microsecond molecular dynamics simulations of proteins using a quasi-equilibrium solvation shell model. J. Chem. Theor. Comput., 16(3):1866–1881, 2020.
4. V. Ovchinnikov, S. Conti, and M. Karplus. A restrained locally enhanced sampling method (rles) for finding free energy minima in complex systems. J. Chem. Phys., 153(12):121103, 2020.
5. U.K. Shigdel, V. Ovchinnikov, S.J. Lee, J.A. Shih, M. Karplus, K. Nam, and G.L. Verdine. The trajectory of intrahelical lesion recognition and extrusion by the human 8-oxoguanine dna glycosylase. Nat. Commun., 11(1):4437, 2020.
6. V. Ovchinnikov, T. A. Stone, C. Deber, and M. Karplus. Structure of the EmrE Multidrug Transporter and Its Use for Inhibitor Peptide Design. Proc. Natl. Acad. Sci. USA, 115(34):E7942, 2018.
7. C. D. Bahl, G. W. Buchko, S.V.S.R.K. Pulavarti, V. Ovchinnikov, E. A. Shaw, S. A. Rettie, P. J. Myler, M. Karplus, T. Szyperski, and D. Baker. Cytosolic expression, solution structures, and molecular dynamics simulation of genetically encodable disulfide-rich de novo designed peptides. Prot. Sci., 27:1611–1623, 2018.
8. V. Ovchinnikov, J. Louveau, J. Barton, M. Karplus, and A. K. Chakraborty. Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies. eLife, 7:e33038, 2018.
9. X. Lu, V. Ovchinnikov, D. Demapan, D. Roston, and Q. Cui. Regulation and plasticity of catalysis in enzymes: Insights from analysis of mechanochemical coupling in myosin. Biochemistry, 56(10):1482–1497, 2017.
10. Y. Meroz, V. Ovchinnikov, and M. Karplus. Coexisting Origins of Subdiffusion in Internal Dynamics of Proteins. Phys. Rev. E, 95:062403, 2017.
11. V. Ovchinnikov, K. Nam, and M. Karplus. A Simple and Accurate Method to Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes. J. Phys. Chem. B, 120:8457–8472, 2016.
12. X. Lu, D. Fang, S. Ito, Y. Okamoto, V. Ovchinnikov, and Q. Cui. QM/MM free energy simulations: recent progress and challenges. Mol. Sim., 42:1056–1078, 2016.
13. P. Ojeda-May, Y. Li, V. Ovchinnikov, and K. Nam. Role of Protein Dynamics in Allosteric Control of the Catalytic Phosphoryl Transfer of Insulin Receptor Kinase. J. Am. Chem. Soc., 137:12454–12457, 2015.
14. V. Ovchinnikov and M. Karplus. Investigations of α-helix-sheet transition pathways in a miniprotein using the finite-temperature string method. J. Chem. Phys., 140:175103, 2014.
15. V. Ovchinnikov, M. Cecchini, and M. Karplus. A Simplified Confinement Method (SCM) for Calculating Absolute Free Energies and Free Energy and Entropy Differences. J. Phys. Chem. B, 117:750–762, 2013
16. V. Ovchinnikov and M. Karplus. Analysis and elimination of a bias in targeted molecular dynamics simulations of conformational transitions: Application to Calmodulin. J. Phys. Chem. B, 116:8584–8603, 2012.
17. V. Ovchinnikov, M. Karplus, and E. Vanden-Eijnden. Free energy of conformational transition paths in biomolecules: The string method and its application to myosin VI. J. Chem. Phys., 134:085103, 2011.
18. V. Ovchinnikov, M. Cecchini, E. Vanden-Eijnden, and M. Karplus. A conformational transition in the myosin VI converter contributes to the variable step size. Biophys. J., 101:2436–2444, 2011.
19. V. Ovchinnikov, B.L. Trout, and M. Karplus. Mechanical coupling in myosin V: A simulation study. J. Mol. Biol., 395:815–833, 2010.
20. B.R. Brooks, C.L. Brooks III, A.D. Mackerell Jr., L. Nilsson, R.J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A.R. Dinner, and et. al. CHARMM: The biomolecular simulation program. J. Comput. Chem., 30:1545–1614, 2009.
21. V. Ovchinnikov, M. M. Choudhari, and U. Piomelli. Numerical simulations of boundary-layer bypass transition due to high-amplitude free-stream turbulence. J. Fluid Mech., 613:135–169, 2008.
22. V. Ovchinnikov, M. M. Choudhari, and U. Piomelli. Numerical simulations of boundary-layer bypass transition induced by a cylinder wake. J. Fluid Mech., 547:413–441, 2006.
Manuscripts Submitted or in Preparation
1. V. Ovchinnikov and M. Karplus. A coarse-grained model of affinity maturation indicates the importance of B-cell receptor avidity in epitope subdominance. in preparation (text available upon request), 2021.
2. K. Sprenger, S. Conti, V. Ovchinnikov, A. Chakraborty, and M. Karplus. Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV. submitted, PLoS Computational Biology, 2021.
3. Y. Meroz, V. Ovchinnikov, and M. Karplus. A simple model of subdiffusion over hierarchical energy landscapes. (text available upon request).
Conference Proceedings
1. Saltzberg, D., Ovchinnikov, V., Dunaway-Mariano, D., Karplus, M. & Allen, K. Ligand Binding and Conformational Change Coupling in the HAD Superfamily. FASEB J. 27, 998.8, 2013
2. Ovchinnikov, V., Piomelli, U. & Choudhari, M. M., 2005 Numerical simulations of bypass transition in flat-plate boundary layers. Bull. Amer. Phys. Soc. 50, p. 114
3. Ovchinnikov, V., Piomelli, U. & Choudhari, M. M. 2005 Numerical simulations of boundary layer bypass transition with leading edge effects. In Proc. 4th Int. Symp. Turbulence and Shear Flow Phenomena, Williamsburg, VA, June 25-27, 2005, 2, p. 425–430
4. Ovchinnikov, V. & Piomelli, U. 2005 Numerical simulation of wake/boundary-layer interaction. The 2005 CEAFM Res. Symp. on Environmental and Appl. Fluid Mech., Johns Hopkins University, Baltimore, MD, May 16, 2005
5. Ovchinnikov, V., Piomelli, U. & Choudhari, M. M., 2004 Inflow conditions for numerical simulations of bypass transition. AIAA Paper 2004-0591
6. Ovchinnikov, V., Piomelli, U. & Choudhari, M. M., 2004 Numerical study of flat-plate boundary layer bypass transition. Bull. Amer. Phys. Soc. 49, p. 22
7. Ovchinnikov, V., Piomelli, U. & Choudhari, M. M., 2003 Numerical simulations of strong wake-boundary layer interaction. Bull. Amer. Phys. Soc. 48, p. 54
8. Piomelli, U., Choudhari, M. M., Ovchinnikov, V. & Balaras, E., 2003 Numerical simulations of wake/boundary layer interactions. AIAA Paper 2003-0975
Selected Presentations
• CHARMM Molecular Modeling Conference, Michgan State University (virtual) : July 17, 2021 Path free energy simulations to understand the mechanism of inhibition of the SARS-CoV2 RNA polymerase by remdesivir
• CHARMM Molecular Modeling Conference, Boston University (virtual) : July 17, 2020 A restrained locally-enhanced samping method for finding free energy minima
• CHARMM Molecular Modeling Conference, Institut Pasteur, Paris : July 12, 2019 GPU acceleration of multigrid Poisson-Boltzmann electrostatics
• CHARMM Molecular Modeling Conference, University of Chicago : July 13, 2018 Biomolecular simulations using a flexible-boundary solvation model
• CHARMM Molecular Modeling Conference, Harvard University : July 15, 2017 Refinement of atomic structure of EmrE transporter and design of inhibitors
• CHARMM Molecular Modeling Conference, Ann Arbor, MI : July 9, 2016 Free energy profiles and reaction rates from restrained simulations of diffusive processes
• CHARMM Molecular Modeling Conference, Vienna, Austria: July 15, 2015 Plasticity of the Rab11/Myosin V cargo interface investigated by molecular simulations
• CHARMM Molecular Modeling Conference, Harvard University: July 18, 2014 Conformational transitions in large complexes using generalized network models
• National Energy Resource Supercomputing Center Annual Meeting, Lawrence Berkeley National Lab : Feb 4, 2014 Conformational change in biology: from amino acids to enzymes to molecular motors
• CHARMM Molecular Modeling Conference, University of Zurich, Switzerland: June 28, 2013 Transition paths and free energies for the α-helix β-sheet isomerization in a G-protein fragment.
• CHARMM Molecular Modeling Conference, National Institutes of Health: July 12, 2012 Simulating conformational transitions with the finite temperature string method
• GPU Programming for Molecular Modeling Workshop, U. of Illinois at Urbana-Champaign: Aug 7, 2010 Poisson-Boltzmann Electrostatics on a GPU
• CHARMM Molecular Modeling Conference, Harvard University: July 22, 2010 Computing the Free Energy of a Conformational Transition in Myosin VI Using the String Method
• Gordon Research Conferences, Colby Sawyer College, NH: June 27, 2008 Simulations of the Pre-Powerstroke/Rigor Transition in the Converter Domain of Myosin VI (poster)
References
Professor Martin Karplus (postdoctoral advisor)
Dept. of Chemistry and Chemical Biology
Harvard University
Professor Ugo Piomelli (dissertation advisor)
Dept. of Mechanical and Materials Engineering
Queens University, Canada
Dr. Anne Houdusse (collaborator)
Group Leader, Structural Motility Laboratory
Institut Curie, Paris
Dr. Marco Cecchini (collaborator)
Laboratory of Molecular Function and Design, ISIS
University of Strasbourg
Professor Eric Vanden-Eijnden (collaborator)
Dept. of Mathematics
New York University, Courant Institute of Mathematical Sciences
Professor Bernhardt Trout (former advisor)
Dept. of Chemical Engineering
Massachusetts Institute of Technology
Dr. Meelan M. Choudhari (collaborator)
Computational Modeling and Simulation Branch
NASA Langley Research Center
Professor Arup Chakraborty (collaborator)
Dept. of Chemical Engineering
Massachusetts Institute of Technology
Professor Qiang Cui (collaborator)
Dept. of Chemistry and Theoretical Chemistry Institute
University of Wisconsin, Madison
Professor Kwangho Nam (collaborator)
Dept. of Chemistry and Biochemistry
University of Texas, Arlington
Dr. Thomas Simonson (colleague)
Dept. of Biology
Director, Laboratoire de Biologie Structurale de la Cellule,
Ecole Polytechnique; France