• 10716 Citations
  • 57 h-Index
1994 …2024

Research output per year

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Personal profile

Research interests

The mission of Dr. Nikolay Dokholyan's laboratory is to develop and apply integrated computational and experimental strategies to understand, sense and control misfolded proteins in order to uncover the etiologies of human neurodegenerative diseases and develop therapeutics to fight them.

The lab aims to understand the molecular disease mechanisms of ALS: How does the misfolding of superoxide dismutase (SOD1) lead to the formation of toxic oligomeric intermediates? Using biochemical and biophysical approaches and innovative computation, the Dokholyan lab determined putative structures of SOD1 oligomers and is currently elucidating the downstream pathways that lead to motorneuron death. Structures of toxic oligomers provide targets for drug discovery, which the lab is pursuing.

Neurodegenerative diseases such as ALS, Alzheimer’s, Huntington’s, Parkinson’s and prion diseases share similar processes associated with protein misfolding and aggregation. These similarities suggest common pathways leading to neuron death that eventually result in a disease. The lab is working toward understanding the general principles of protein misfolding in neurodegenerative diseases through computational and experimental approaches.

To sense and control protein conformations, the lab is working toward development of genetically-encoded proteins that bind and report rare/intermediate conformations of target molecules or alter their state using drugs or light.

One of the critical components of the lab's integrative research is drug discovery, focusing on both biological therapeutics and small molecule screening. The lab developed a fully flexible docking algorithm, MedusaDock, that allows for virtual screening of compounds and is is an important asset for small molecule drug discovery efforts.

The lab has developed novel approaches to molecular dynamics simulations and modeling, allowing studies of biological molecules at time scales relevant to biological systems. These approaches synergistically integrate rapid dynamics simulations, molecular modeling and design, and biochemical and cellular biology experiments, allowing for significant strides in understanding the etiology of misfolding diseases.

Professional information

Fellow, American Academy for the Advancement of Science (2019)

Fellow, American Physical Society (2013)

Education/Academic qualification

Biophysics, National Institutes of Health Postdoctoral Fellowship, Harvard University

19992002

Physics, PhD, Boston University

… → 1999

Physics, MS, Moscow Institute of Physics and Technology

… → 1994

Physics, BS, Moscow Institute of Physics and Technology

… → 1992

External positions

Editor in Chief, Research and Reports in Biochemistry

Jan 1 2011Jan 1 2016

Editor in Chief, Research and Reports in Biochemistry

20112016

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Projects

  • Research Output

    Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent

    Dinavahi, S. S., Gowda, R., Gowda, K., Bazewicz, C. G., Chirasani, V. R., Battu, M. B., Berg, A., Dokholyan, N. V., Amin, S. & Robertson, G. P., Feb 1 2020, In : Molecular cancer therapeutics. 19, 2, p. 447-459 13 p.

    Research output: Contribution to journalArticle

  • Ligand-induced disorder-to-order transitions characterized by structural proteomics and molecular dynamics simulations

    Makepeace, K. A. T., Brodie, N. I., Popov, K. I., Gudavicius, G., Nelson, C. J., Petrotchenko, E. V., Dokholyan, N. V. & Borchers, C. H., Jan 16 2020, In : Journal of Proteomics. 211, 103544.

    Research output: Contribution to journalArticle

    Open Access
  • Single-channel properties of skeletal muscle ryanodine receptor pore Δ4923FF4924 in two brothers with a lethal form of fetal akinesia

    Xu, L., Harms, F. L., Chirasani, V. R., Pasek, D. A., Kortüm, F., Meinecke, P., Dokholyan, N. V., Kutsche, K. & Meissner, G., May 2020, In : Cell Calcium. 87, 102182.

    Research output: Contribution to journalArticle

  • A central core disease mutation in the Ca2+-binding site of skeletal muscle ryanodine receptor impairs single-channel regulation

    Chirasani, V. R., Xu, L., Addis, H. G., Pasek, D. A., Dokholyan, N. V., Meissner, G. & Yamaguchi, N., Aug 2019, In : American Journal of Physiology - Cell Physiology. 317, 2, p. C358-C365

    Research output: Contribution to journalArticle

  • 2 Scopus citations

    Allostery in Its Many Disguises: From Theory to Applications

    Wodak, S. J., Paci, E., Dokholyan, N. V., Berezovsky, I. N., Horovitz, A., Li, J., Hilser, V. J., Bahar, I., Karanicolas, J., Stock, G., Hamm, P., Stote, R. H., Eberhardt, J., Chebaro, Y., Dejaegere, A., Cecchini, M., Changeux, J. P., Bolhuis, P. G., Vreede, J., Faccioli, P. & 19 others, Orioli, S., Ravasio, R., Yan, L., Brito, C., Wyart, M., Gkeka, P., Rivalta, I., Palermo, G., McCammon, J. A., Panecka-Hofman, J., Wade, R. C., Di Pizio, A., Niv, M. Y., Nussinov, R., Tsai, C. J., Jang, H., Padhorny, D., Kozakov, D. & McLeish, T., Apr 2 2019, In : Structure. 27, 4, p. 566-578 13 p.

    Research output: Contribution to journalReview article

  • 23 Scopus citations