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)
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Biophysics, National Institutes of Health Postdoctoral Fellowship, Department of Chemistry and Chemical Biology, 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
2011 → 2016
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Collaborations and top research areas from the last five years
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Discovery of functionally selective dopamine ligands for age-related cognitive decline
Yang, Y. (PI), Dokholyan, N. (CoPI) & Mailman, R. (CoPI)
6/1/24 → 5/31/26
Project: Research project
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AI-based Mapping of Complex Cannabis Extracts in Pain Pathways
Vrana, K. (PI) & Dokholyan, N. (CoPI)
National Center for Complementary and Integrative Health
2/14/23 → 11/30/25
Project: Research project
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FET:Medium: Drug discovery using quantum machine learning
Ghosh, S. (PI) & Dokholyan, N. (CoPI)
10/1/22 → 9/30/26
Project: Research project
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Nanoscale programing of celluar and physiological phenotypes
Dokholyan, N. (PI)
National Institute of General Medical Sciences
1/1/20 → 4/30/26
Project: Research project
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Discovery of functionally selective dopamine ligands for age-related cognitive decline
Yang, Y. (PI), Dokholyan, N. (CoPI) & Mailman, R. (CoPI)
6/1/21 → 5/31/24
Project: Research project
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Autonomous Nucleic Acid and Protein Nanocomputing Agents Engineered to Operate in Living Cells
Panigaj, M., Basu Roy, T., Skelly, E., Chandler, M. R., Wang, J., Ekambaram, S., Bircsak, K., Dokholyan, N. V. & Afonin, K. A., Jan 21 2025, In: ACS nano. 19, 2, p. 1865-1883 19 p.Research output: Contribution to journal › Review article › peer-review
Open Access3 Scopus citations -
CANDI: a web server for predicting molecular targets and pathways of cannabis-based therapeutics
Ekambaram, S., Wang, J. & Dokholyan, N. V., Dec 2025, In: Journal of Cannabis Research. 7, 1, 13.Research output: Contribution to journal › Article › peer-review
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Leveraging Transfer Learning for Predicting Protein-Small-Molecule Interaction Predictions
Wang, J. & Dokholyan, N. V., Apr 14 2025, In: Journal of Chemical Information and Modeling. 65, 7, p. 3262-3269 8 p.Research output: Contribution to journal › Article › peer-review
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RNA-Puzzles Round V: blind predictions of 23 RNA structures
Bu, F., Adam, Y., Adamiak, R. W., Antczak, M., de Aquino, B. R. H., Badepally, N. G., Batey, R. T., Baulin, E. F., Boinski, P., Boniecki, M. J., Bujnicki, J. M., Carpenter, K. A., Chacon, J., Chen, S. J., Chiu, W., Cordero, P., Das, N. K., Das, R., Dawson, W. K. & DiMaio, F. & 79 others, , Feb 2025, In: Nature methods. 22, 2, p. 399-411 13 p., 2871.Research output: Contribution to journal › Article › peer-review
Open Access10 Scopus citations -
The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives
Ekambaram, S., Arakelov, G. & Dokholyan, N. V., 2025, (Accepted/In press) In: Journal of Molecular Biology. 169060.Research output: Contribution to journal › Review article › peer-review
Prizes
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Michael Hooker Distinguished Professor in Biochemistry and Biophysics
Dokholyan, N. (Recipient), 2013
Prize
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