Nikolay Dokholyan, PhD

Nikolay Dokholyan, PhD Michael Hooker Distinguished Professor of Biochemistry & Biophysics

Director, Center for Computational and Systems Biology
Graduate Director, Program in Cellular and Molecular Biophysics
PHD - Boston University


  • Michael Hooker Distinguished Professorship, 2014
  • American Physical Society Fellow, 2013
  • March of Dimes Basil O'Connor Starter Scholar Research Award, 2004-2006


Molecular etiologies of human diseases

My laboratory focuses on understanding etiologies of human diseases, such as cystic fibrosis (CF), amyotrophic lateral sclerosis (ALS), and conditions, such as hyperalgesia. My lab has utilized several integrated computational and experimental strategies to understand, sense (recognize and report), and control aberrant biological molecules, and uncover etiologies of human diseases. We have developed approaches to molecular structural modeling and dynamic simulations, allowing study of structure and dynamics of biological molecules at time scales relevant to biological systems. These approaches uniquely distinguish my laboratory from others because they integrate rapid physical dynamics simulations, experiments, and molecular modeling and design, allowing us to make significant breakthroughs in understanding etiologies of CF and ALS. The translational research in my laboratory is based on our developed methodologies described below.

Methodologies. Molecular structure and dynamics underlies all biological processes. Most research in biomedical fields is directly or indirectly associated with molecular behavior. In the field of biochemistry, experimental approaches have been directly targeting these molecular properties, albeit within a specific “window” of observable length and time scales. Computational approaches can offer much wider windows, but present only hypotheses about the system rather than “real” observables. Integrated computational and experimental approaches, therefore, present unparalleled strategies for exploring biological systems, a philosophy that has guided us in my laboratory.

Perhaps the most outstanding challenge in computational biology is sampling of molecular conformational states. Most research in my laboratory has been dedicated to solving this critical problem. We achieved this goal by developing rapid discrete molecular dynamics simulations, novel and unique in the level of accuracy molecular docking algorithm that we have already used to find novel lead compounds to treat CF and reduce chronic and acute pain (in both cases these compounds are been pursued by biotech companies).  We are currently pursuing understanding of other human diseases and developing novel pharmaceutical strategies to combat them, and actually searching for compounds using a combination of virtual drug screening and experiment. Application of these tools also allows rational design of proteins that can control other proteins in living cells and organisms. These tools are becoming invaluable resources that enables decoupling cellular networks, as well understanding the impact of a specific protein on the phenotype of an organism.

RECENT PUBLICATIONS  pubmed.png (click for Full Publication List)

  • Dagliyan, O., Shirvanyants, D., Karginov, A., Ding, F., Chandrasekaran, S. N., Freisinger, C. M.,  Smolen, G. A., Huttenlocher, A.,  Hahn, K. M., and Dokholyan, N. V., “Rational design of a novel protein for allosteric control of kinases in living organisms” Proceedings of the National Academy of Sciences USA, 110: 6800-6804 (2013)
  • Kummer, L., Hsu, C.W., Dagliyan, O., Kaufholz, M., Zimmermann, B., Dokholyan, N. V., Hahn, K. M., Plückthun, A., “Knowledge-based design of a biosensor to quantify localized ERK activation in living cells” Chemistry & Biology, 20: 847- 856 (2013)
  • Cole, D. I., Legassie, J. D., Bonifacio, L. N., Sekaran, V. G., Ding, F., Dokholyan, N. V*., and  Jarstfer, M. B.,* “New models of tetrahymena telomerase RNA from experimentally derived constraints and modeling” Journal of the American Chemical Society, 134: 20070–20080 (2012)
  • Sparta, M., Ding, F., Shirvanyants, D., Dokholyan*, N. V., and Alexandrova*A. N., “Hybrid dynamics simulation engine for metalloproteins” Biophysical Journal, 103: 767-776 (2012)
  • Redler, R. L., and Dokholyan, N. V., “The complex molecular biology of amyotrophic lateral sclerosis (ALS).” Progress in Molecular Biology and Translational Science, 107: 215-262 (2012)
  • Ding, F.,  Lavender, C. A., Weeks, K. M.  and Dokholyan, N. V., "Three- dimensional RNA structure refinement by hydroxyl radical probing" Nature Methods, 9: 603-608 (2012)
  • Tsao, D., Wieskopf, J. S., Rashid, N., Sorge, R. E., Redler, R. L., Segall, S. K., Mogil, J. S., Maixner, W., Dokholyan, N. V., and Diatchenko, L., “Serotonin- induced hypersensitivity via inhibition of catechol O-methyltransferase activity”, Molecular Pain, 8: 25 (2012)
  • Proctor, E. A., Yin, S., Tropsha, A., Dokholyan, N. V., “Discrete molecular dynamics distinguishes native-like binding poses from decoys in difficult targets” Biophysical Journal, 102: 144-151 (2012)
  • Shirvanyants, D., Ding, F., Tsao, D., Ramachandran, S., Dokholyan, N. V., "DMD: an efficient and versatile simulation method for fine protein characterization" The Journal of Physical Chemistry B, 116: 8375-8382 (2012)
  • Ding, F., Furukawa, Y., Nukina, N., and Dokholyan, N. V., “Local unfolding of Cu, Zn Superoxide Dismutase monomer determines the morphology of fibrillar aggregates” Journal of Molecular Biology, 421: 548-560 (2012)
  • Nakayama, T., Butler, J. S., Sehgal, A., Severgnini, M., Racie, T., Sharman J., Ding, F., Morskaya, S. S., Brodsky, J., Tchangov, L., Kosovrasti, V., Meys, M., Nechev, L., Wang, G., Peng, C. G., Fang, Y., Maier, M., Rajeev, K. G., Li, R., Hettinger, J., Barros, S., Clausen, V., Zhang, X., Wang, Q., Hutabarat, R., Dokholyan, N. V., Wolfrum, C., Manoharan, M., Kotelianski, V., Stoffel, M. and Sah, D. W. Y. "Harnessing a Physiologic Mechanism for siRNA Delivery with Mimetic Lipoprotein Particles", Molecular Therapyin press (2012)
  • Serohijos, A. W. R., Yin, S., Ding, F.,  Gauthier, J., Gibson, D. G., Maixner, W., Dokholyan, N. V. *, and Diatchenko, L. *, “Structural basis for μ-opioid receptor binding and activation” Structure, 19: 1683-1690 (2011)
  • Dagliyan, O., Proctor, E. A., D'Auria, K., Ding, F., and Dokholyan, N. V., “Structural and dynamic determinants of protein-peptide recognition” Structure, 19: 1837–1845 (2011) [Cover article]
  • Redler, R. L.,  Wilcox, K. C., Proctor, E. A., Fee, L., Caplow, M. and Dokholyan, N. V. "Glutathionylation at Cys 111 triggers dissociation of wild type and FALS mutant SOD1 dimers" Biochemistry, 50: 7057-7066 (2011)
  • Ding, F., Yin, S.  and Dokholyan, N. V., "Rapid flexible docking using a stochastic rotamer library of ligands" Journal of Chemical Information and Modeling, 50: 1623-1632 (2010)
  • Karginov, A. V., Ding, F., Kota, P., Dokholyan, N. V. *, and Hahn, K. M. *, "Engineered allosteric activation of kinases in living cells" Nature Biotechnology, 28: 743–748 (2010)
  • Aleksandrov, A. A., Kota, P., Aleksandrov, L. A., He, L., Jensen, T., Cui, L., Gentzsch, M., Dokholyan, N. V., and Riordan, J. R. "Regulatory insertion removal restores maturation, stability and function of ΔF508 CFTR", Journal of Molecular Biology, 401:194-210 (2010)
  • Kota, P., Summers, D., Ren, H.Y., Cyr, D. M., and Dokholyan, N. V., “Identification of a consensus motif in substrates bound by a Type I Hsp40” Proceedings of the National Academy of Sciences USA, 106: 11073-11078 (2009)
  • Wilcox, K., Zhou, L., Jordon, J., Huang, Y., Yu, Y., Redler, R. L., Chen, X., Caplow, M., and  Dokholyan, N. V., “Modifications of SOD1 in human erythrocytes: A possible role in ALS”, Journal of Biological Chemistry, 284: 13940-13947 (2009)
  • Yin, S., Proctor, E. A., Lugovskoy, A. A. and Dokholyan, N. V. "Fast screening of protein surfaces using geometric invariant fingerprints", Proceedings of the National Academy of Sciences USA, 106:16622-16626 (2009)
  • Yin, S., Biedermannova, L., Vondrasek, J., and Dokholyan, N. V., "MedusaScore: An accurate force-field based scoring function for virtual drug screening", Journal of Chemical Information and Modeling, 48:1656-1662 (2008)
  • Ding, F., Tsao, D., Nie, H., and Dokholyan, N. V. "Ab initio folding of proteins with all-atom discrete molecular dynamics", Structure, 16:1010-1018 (2008)
  • Hao, J., Serohijos, A. W. R., Newton, G., Tassone, G., Wang, Z., Sgroi, D. C., Dokholyan, N. V.*, and Basilion, J. P.*, "Identification of peptide ligands to CRIP1, a novel biomarker for cancers", Public Library of Science Computational Biology, 4:e1000138 (2008)
  • Yin, S., Ding, F., and Dokholyan, N. V. "Eris: An automated estimator of protein stability", Nature Methods, 4:466-467 (2007)


    Dokholyan Lab Website

    120 Mason Farm Rd,
    Campus Box # 7260
    3097 Genetic Medicine
    Chapel Hill, NC 27599
    Office: 919-843-2513

    Lab Rooms: 3100C-D Genetic Med
    Lab Phone: 919-966-3137