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

Jan 1 2011Jan 1 2016

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.

  • 2 Similar Profiles
Molecular Dynamics Simulation Medicine & Life Sciences
Proteins Medicine & Life Sciences
Mutation Medicine & Life Sciences
RNA Medicine & Life Sciences
Protein Folding Medicine & Life Sciences
Molecular dynamics Chemical Compounds
Cystic Fibrosis Transmembrane Conductance Regulator Medicine & Life Sciences
Thermodynamics Medicine & Life Sciences

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

Projects 1999 2021

Allosteric Regulation
Protein Interaction Maps
Guanine
Proteins
Guanosine Triphosphate
Screening
Ligands
Pharmaceutical Preparations
Proteins
Chemical compounds
Vinculin
Actins
Null Lymphocytes
Adherens Junctions
Focal Adhesions
Proteins
Molecular dynamics
Machine design
Conformations
Amino acids
Epitopes
Carbohydrates
HIV
Viruses
Glycosylation

Research Output 1994 2019

5 Citations (Scopus)

Allostery in Its Many Disguises: From Theory to Applications

Wodak, S. J., Paci, E., Dokholyan, N., 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 othersOrioli, 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

Allosteric Regulation
Biological Phenomena
Education
Drug Design
Signal Transduction

Cardiomyopathy Mutations in Metavinculin Disrupt Regulation of Vinculin-Induced F-Actin Assemblies

Sarker, M., Lee, H. T., Mei, L., Krokhotin, A., de los Reyes, S. E., Yen, L., Costantini, L. M., Griffith, J., Dokholyan, N., Alushin, G. M. & Campbell, S. L., Apr 5 2019, In : Journal of Molecular Biology. 431, 8, p. 1604-1618 15 p.

Research output: Contribution to journalArticle

Vinculin
Cardiomyopathies
Actins
Mutation
Dimerization

Conformational ensemble of native α-synuclein in solution as determined by short-distance crosslinking constraint-guided discrete molecular dynamics simulations

Brodie, N. I., Popov, K. I., Petrotchenko, E. V., Dokholyan, N. & Borchers, C. H., Mar 1 2019, In : PLoS computational biology. 15, 3, e1006859.

Research output: Contribution to journalArticle

Open Access
Synucleins
Discrete Dynamics
molecular dynamics
protein structure
Molecular Dynamics Simulation

Engineering proteins for allosteric control by light or ligands

Dagliyan, O., Dokholyan, N. & Hahn, K. M., Jun 1 2019, In : Nature Protocols. 14, 6, p. 1863-1883 21 p.

Research output: Contribution to journalArticle

Protein Engineering
Ligands
Light
Guanine
Sirolimus

MedusaDock 2.0: Efficient and Accurate Protein-Ligand Docking with Constraints

Wang, J. & Dokholyan, N., Jun 24 2019, In : Journal of Chemical Information and Modeling. 59, 6, p. 2509-2515 7 p.

Research output: Contribution to journalArticle

Ligands
drug
Proteins
efficiency
energy