• 9651 Citations
  • 55 h-Index
1994 …2021
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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 Physical Society (2013)

Education/Academic qualification

Biophysics, National Institutes of Health Postdoctoral Fellowship, Harvard University


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


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Projects 1999 2021

Engineering allostery for in vivo protein control

Dokholyan, N.

National Institutes of Health


Project: Research projectResearch Project

Allosteric Regulation
Protein Interaction Maps
Guanosine Triphosphate
Pharmaceutical Preparations
Chemical compounds

Mechanisms of vinculin activation and force transmission

Dokholyan, N. & Campbell, S.

National Institutes of Health


Project: Research projectResearch Project

Null Lymphocytes
Adherens Junctions
Focal Adhesions


Dokholyan, N.

National Institutes of Health

9/1/99 → …

Project: Research projectPostdoctoral Individual National Research Service Award

Molecular dynamics
Machine design
Amino acids

Immunogen Design to Target Carbohydrate-Occluded Epitopes on the HIV envelope

Dokholyan, N. & Swanstrom, R.

National Institutes of Health


Project: Research projectResearch Project


Research Output 1994 2018

Ca2-mediated activation of the skeletal-muscle ryanodine receptor ion channel

Xu, L., Chirasani, V. R., Carter, J. S., Pasek, D. A., Dokholyan, N., Yamaguchi, N. & Meissner, G., Jan 1 2018, In : Journal of Biological Chemistry. 293, 50, p. 19501-19509 9 p.

Research output: Contribution to journalArticle

Ryanodine Receptor Calcium Release Channel
Ion Channels
Skeletal Muscle
Chemical activation

Computational design of chemogenetic and optogenetic split proteins

Dagliyan, O., Krokhotin, A., Ozkan-Dagliyan, I., Deiters, A., Der, C. J., Hahn, K. M. & Dokholyan, N., Dec 1 2018, In : Nature communications. 9, 1, 4042.

Research output: Contribution to journalArticle

Biological Phenomena
1 Citations

G4941K substitution in the pore-lining S6 helix of the skeletal muscle ryanodine receptor increases RyR1 sensitivity to ytosolic and luminal Ca2+

Xu, L., Mowrey, D. D., Chirasani, V. R., Wang, Y., Pasek, D. A., Dokholyan, N. & Meissner, G., Jan 1 2018, In : Journal of Biological Chemistry. 293, 6, p. 2015-2028 14 p.

Research output: Contribution to journalArticle

S 6
Ryanodine Receptor Calcium Release Channel
Skeletal Muscle
3 Citations

High-speed atomic force microscopy reveals structural dynamics of α -synuclein monomers and dimers

Zhang, Y., Hashemi, M., Lv, Z., Williams, B., Popov, K. I., Dokholyan, N. & Lyubchenko, Y. L., Mar 28 2018, In : Journal of Chemical Physics. 148, 12, 123322.

Research output: Contribution to journalArticle

dynamic structural analysis
Structural dynamics
Atomic force microscopy
1 Citations

Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis

Zhu, C., Beck, M. V., Griffith, J. D., Deshmukh, M. & Dokholyan, N., May 1 2018, In : Proceedings of the National Academy of Sciences of the United States of America. 115, 18, p. 4661-4665 5 p.

Research output: Contribution to journalArticle

Amyotrophic Lateral Sclerosis
Cell Survival
Motor Neurons
Neurodegenerative Diseases