• 9472 Citations
  • 55 h-Index
1994 …2021
If you made any changes in Pure, your changes will be visible here soon.

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

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

20112016

Fingerprint Fingerprint is based on mining the text of the experts' scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

  • 3 Similar Profiles
Molecular Dynamics Simulation Medicine & Life Sciences
Proteins Medicine & Life Sciences
Protein folding Chemical Compounds
Molecular dynamics Chemical Compounds
Protein Folding Medicine & Life Sciences
Thermodynamics Medicine & Life Sciences
Mutation Medicine & Life Sciences
RNA Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects 1999 2021

Engineering allostery for in vivo protein control

Dokholyan, N.

National Institutes of Health

5/1/173/31/21

Project: Research projectResearch Project

Allosteric Regulation
Protein Interaction Maps
Guanine
Proteins
Guanosine Triphosphate
Screening
Ligands
Pharmaceutical Preparations
Proteins
Chemical compounds

Mechanisms of vinculin activation and force transmission

Dokholyan, N. & Campbell, S.

National Institutes of Health

4/1/163/31/20

Project: Research projectResearch Project

Vinculin
Actins
Null Lymphocytes
Adherens Junctions
Focal Adhesions

TOWARDS MORE REALISTIC DESIGN OF PROTEINS

Dokholyan, N.

National Institutes of Health

9/1/99 → …

Project: Research projectPostdoctoral Individual National Research Service Award

Proteins
Molecular dynamics
Machine design
Conformations
Amino acids

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

Dokholyan, N. & Swanstrom, R.

National Institutes of Health

7/1/126/30/17

Project: Research projectResearch Project

Epitopes
Carbohydrates
HIV
Viruses
Glycosylation

Research Output 1994 2018

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. V., Dec 1 2018, In : Nature Communications. 9, 1, 4042.

Research output: Contribution to journalArticle

protein
hypothesis testing
biological processes
ligand
prediction

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
Linings
Muscle
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

alpha-Synuclein
dynamic structural analysis
Structural dynamics
Dimers
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. V., 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
Poisons
Neurodegenerative Diseases

Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator

Wang, C., Aleksandrov, A. A., Yang, Z., Forouhar, F., Proctor, E. A., Kota, P., An, J., Kaplan, A., Khazanov, N., Boël, G., Stockwell, B. R., Senderowitz, H., Dokholyan, N., Riordan, J. R., Brouillette, C. G. & Hunt, J. F., Jan 1 2018, In : Journal of Biological Chemistry. 293, 46, p. 17685-17704 20 p.

Research output: Contribution to journalArticle

Electrophysiology
Cystic Fibrosis Transmembrane Conductance Regulator
Nucleotides
Stabilization
Ligands