Projects per year
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
1999 → 2002
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 2011 → Jan 1 2016Editor in Chief, Research and Reports in Biochemistry
2011 → 2016Fingerprint Dive into the research topics where Nikolay Dokholyan is active. These topic labels come from the works of this person. Together they form a unique fingerprint.
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Projects
Nanoscale programing of cellular and physiological phenotypes
1/1/20 → 12/31/24
Project: Research project
Integrating cheminformatics and molecular simulations for virtual drug screening
8/15/16 → 5/31/20
Project: Research project
Mechanisms of vinculin activation and force transmission
Dokholyan, N. & Campbell, S.
4/1/16 → 3/31/20
Project: Research project
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 journal › Article
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 journal › Article
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 journal › Article
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-C365Research output: Contribution to journal › Article
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, , Apr 2 2019, In : Structure. 27, 4, p. 566-578 13 p.Research output: Contribution to journal › Review article
23
Scopus
citations
Prizes
Michael Hooker Distinguished Professor in Biochemistry and Biophysics
Nikolay Dokholyan (Recipient), 2013
Prize