Igor Vorobyov, Ph.D.
4133 Tupper Hall
Research in our laboratory focuses on using computer modeling and simulation techniques, such as molecular docking and molecular dynamics, to study interactions of drugs and other small molecules with membrane associated and water soluble proteins of biomedical significance. In particular, we have been using atomistic computational models to reveal molecular mechanisms of voltage-gated sodium and potassium channel ion conduction and drug binding: Voltage-gated sodium (NaV), potassium (KV) and calcium (CaV) channels are integral membrane transport proteins, which are crucial components of electrical signaling in excitable cells and are key targets for therapeutics used for cardiac and neurological disorders.
In a collaborative NIH funded study led by Prof. Colleen Clancy we use multi-scale modeling approaches to develop in silico predictive safety pharmacology for drugs, affecting functions of cardiac voltage-gated ion channel proteins KV11.1 (also known as hERG), NaV1.5 and CaV1.2. Channel state-specific drug affinities, entry and egress kinetics are computed from our all-atom simulations and used to populate multi-scale functional models developed in Prof. Clancy's laboratory. These studies are performed in collaboration with Profs. Vladimir Yarov-Yarovoy, Jon Sack, Kazuharu Furutani, Heike Wulff and Eleonora Grandi at UC Davis, Sergei Noskov at University of Calgary (Canada) and Toby Allen at RMIT University (Australia).
In another collaborative project with Prof. Fredric Gorin at UC Davis, we are working on potential anti-cancer drug testing via predicting their binding conformations and affinities to a protein complex UPA/PAI-1, over-expressed in highly malignant cancer cells. Molecular docking and molecular dynamics simulations have been used to correlate drug protein binding to anti-tumor activities, predicted by experimental studies in Prof. Gorin's laboratory.
An up-to-date publication list and citation information: Google Scholar
DeMarco, K. R., Bekker, S., Clancy, C. E., Noskov, S. Y., Vorobyov, I. “Digging into lipid membrane permeation for cardiac ion channel blocker d-sotalol with all-atom simulations.” Frontiers in Pharmacology 2018, 9, 26.
Vorobyov, I., Clancy, C. E. (2018). “Sex, drugs, and funky rhythms.” Heart Rhythm 2018, 15, 485-486.
Yang, P.-C., Perissinotti, L.L., López-Redondo, F., Wang, Y., DeMarco, K.R., Mao-Tsuen, J., Vorobyov, I., Harvey, R.D., Kurokawa, J., Noskov, S.Y., Clancy, C.E. “A multiscale computational modeling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias” Journal of Physiology 2017, 595, 4695-4723.
Vorobyov, I., Kim, I., Chu, Z. T., Warshel, A. “Refining the treatment of membrane proteins by coarse-grained models” Proteins: Structure, Function, and Bioinformatics 2016, 84, 92-117.
Boiteux, C. *, Vorobyov, I.*, French, R. J., French, C., Yarov-Yarovoy, V., Allen, T. W. “Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel” Proceedings of the National Academy of Sciences of the United States of America. (PNAS) 2014, 111, 13057–13062 (*equal author contribution)
Boiteux, C., Vorobyov, I., Allen, T. W. “Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel.” Proceedings of the National Academy of Sciences of the United States of America. (PNAS) 2014, 111, 3454-3459.
Vorobyov, I., Olson, T. E., Kim, J. H., Koeppe II, R. E., Andersen, O. S., Allen, T. W. “Ion-induced defect permeation of lipid membranes”. Biophysical Journal 2014, 106, 586-597.
Vorobyov, I., Bennett, D., Tieleman, D. P., Allen, T. W., Noskov, S. “The role of atomic polarization in the thermodynamics of chloroform partitioning to lipid bilayers.” Journal of Chemical Theory and Computation 2012, 8, 618-628.
Li, L., Vorobyov, I., Allen, T. W. “The role of membrane thickness in charged protein-lipid interactions.” Biochimica et Biophysica Acta - Biomembranes 2012, 1818, 135-145.
Vorobyov, I., Allen, T. W. “On the role of anionic lipids in charged protein interactions with membranes.” Biochimica et Biophysica Acta - Biomembranes 2011, 1808, 1673-1683.
Vorobyov, I., Allen, T. W. “The electrostatics of solvent and membrane interfaces and the role of electronic polarizability.” Journal of Chemical Physics 2010, 132, 185101. (Editor’s choice 2010)
Vorobyov, I., Bekker, B., Allen, T. W. “The electrostatics of deformable lipid membranes.” Biophysical Journal 2010, 98, 2904-2913.
Klauda, J. B., Venable, R. M., Freites, J. A., O’Connor, J. W., Tobias, D. J., Mondragon-Ramirez, C., Vorobyov, I., MacKerell, Jr., A. D., Pastor, R. W. “Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.” Journal of Physical Chemistry B 2010, 114, 7830-7843.
Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., MacKerell Jr., A.D. “CHARMM General Force Field (CGenFF): A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.” Journal of Computational Chemistry 2010, 31, 671-690.
Vorobyov, I., Allen, T. W. “Molecular dynamics computations for proteins: a case study in membrane ion permeation.” In Handbook of Molecular Biophysics: Methods and Applications Bohr, H. G, Ed. WILEY-VCH Verlag GmbH.: Weinheim, 2009, 1034 pp.
Vorobyov, I., Li, L. B., Allen, T. W. “Assessing atomistic and coarse-grained force fields for protein-lipid interactions: the formidable challenge of an ionizable side chain in a membrane.” Journal of Physical Chemistry B 2008, 112, 9588-9602.
Li, L. B., Vorobyov, I., Allen, T. W. “Potential of mean force and pKa profile calculation for a lipid membrane-exposed Arg side chain.” Journal of Physical Chemistry B 2008, 112, 9574-9587.
Li, L. B., Vorobyov, I., MacKerell, A. D., Jr., Allen, T. W. “Is arginine charged in a membrane?” Biophysical Journal 2008, 94, L11-L13.
Vorobyov, I., Anisimov, V. M., Greene, S., Venable, R. M., Moser, A., Pastor, R. W., MacKerell, A. D., Jr. “Additive and classical Drude polarizable force fields for linear and cyclic ethers.” Journal of Chemical Theory and Computation 2007, 3, 1120-1133.
Vorobyov, I. V., Anisimov V., MacKerell, A. D., Jr. “Polarizable empirical force field for alkanes based on the classical Drude oscillator model.” Journal of Physical Chemistry B 2005, 109, 18988-18999.
Anisimov, V. M., Lamoureux, G., Vorobyov, I. V., Huang, N., Roux, B., MacKerell, A. D., Jr. “Determination of electrostatic parameters for a polarizable force field based on the classical Drude oscillator.” Journal of Chemical Theory and Computation 2005, 1, 153-168.
Yappert, M. C., Rujoi, M., Borchman, D., Vorobyov, I., Estrada, R. “Glycero- versus sphingo-phospholipids: Correlations with human and non-human mammalian lens growth.” Experimental Eye Research 2003, 76, 725-734.
Vorobyov, I., Yappert, M. C., DuPré, D. B. “Energetic and Topological Analyses of Cooperative σH- and πH-Bonding Interactions”. Journal of Physical Chemistry A 2002, 106, 10691-10699.
Vorobyov, I., Yappert, M. C. and DuPré, D. B. “Hydrogen bonding in monomers and dimers of 2-aminoethanol”. Journal of Physical Chemistry A 2002, 106, 668-679.
Talbott, C. M., Vorobyov, I., Borchman, D., Taylor, K. G., DuPré, D. B., Yappert, M. C. “Conformational studies of sphingolipids by NMR spectroscopy. II. Sphingomyelin” Biochimica et Biophysica Acta - Biomembranes 2000, 1467, 326-337.