Researcher Profile

Researcher Profile

Nikolay Dokholyan, PhD, MS

Nikolay Dokholyan, PhD, MS

G. Thomas Passananti Professor and Vice Chair for Research, Department of Pharmacology
G. Thomas Passananti Professor, Department of Biochemistry and Molecular Biology
Scientific Program:Experimental Therapeutics

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.

  • Proteins
  • Molecular Dynamics Simulation
  • Mutation
  • RNA
  • Ligands
  • Protein Folding
  • Thermodynamics
  • Amyotrophic Lateral Sclerosis
  • Peptides
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA
  • Amino Acids

Recent Publications


Chirasani, VR, Xu, L, Addis, HG, Pasek, DA, Dokholyan, N, Meissner, G & Yamaguchi, N 2019, 'A central core disease mutation in the Ca2+-binding site of skeletal muscle ryanodine receptor impairs single-channel regulation', American Journal of Physiology - Cell Physiology, vol. 317, no. 2, pp. C358-C365.
Dagliyan, O, Dokholyan, N & Hahn, KM 2019, 'Engineering proteins for allosteric control by light or ligands', Nature Protocols, vol. 14, no. 6, pp. 1863-1883.
Sapienza, PJ, Popov, KI, Mowrey, DD, Falk, BT, Dokholyan, N & Lee, AL 2019, 'Inter-Active Site Communication Mediated by the Dimer Interface β-Sheet in the Half-the-Sites Enzyme, Thymidylate Synthase', Biochemistry, vol. 58, no. 30, pp. 3302-3313.
Wang, J, Williams, B, Chirasani, VR, Krokhotin, A, Das, R & Dokholyan, N 2019, 'Limits in accuracy and a strategy of RNA structure prediction using experimental information', Nucleic acids research, vol. 47, no. 11, pp. 5563-5572.
Proctor, EA, Mowrey, DD & Dokholyan, N 2019, 'β-Methylamino-L-alanine substitution of serine in SOD1 suggests a direct role in ALS etiology', PLoS computational biology, vol. 15, no. 7, e1007225.


Shobair, M, Popov, KI, Dang, YL, He, H, Jackson Stutts, M & Dokholyan, N 2018, 'Mapping allosteric linkage to channel gating by extracellular domains in the human epithelial sodium channel' Journal of Biological Chemistry, vol. 293, no. 10, pp. 3675-3684.




Hadi-Alijanvand, H, Proctor, EA, Ding, F, Dokholyan, N & Moosavi-Movahedi, AA 2016, 'A hidden aggregation-prone structure in the heart of hypoxia inducible factor prolyl hydroxylase', Proteins: Structure, Function and Bioinformatics, vol. 84, no. 5, pp. 611-623.
Jacob, RB, Michaels, KC, Anderson, CJ, Fay, JM & Dokholyan, N 2016, 'Harnessing Nature's Diversity: Discovering organophosphate bioscavenger characteristics among low molecular weight proteins', Scientific reports, vol. 6, 37175.


Williams, B, Convertino, M, Das, J & Dokholyan, N 2015, 'ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations' PLoS computational biology, vol. 11, no. 10, e1004359.
Meloto, CB, Segall, SK, Smith, S, Parisien, M, Shabalina, SA, Rizzatti-Barbosa, CM, Gauthier, J, Tsao, D, Convertino, M, Piltonen, MH, Slade, GD, Fillingim, RB, Greenspan, JD, Ohrbach, R, Knott, C, Maixner, W, Zaykin, D, Dokholyan, N, Reenila, I, Mannisto, PT & Diatchenko, L 2015, 'COMT gene locus: New functional variants', Pain, vol. 156, no. 10, pp. 2072-2083.
Krokhotin, A & Dokholyan, N 2015, Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models. in Methods in Enzymology. Methods in Enzymology, vol. 553, Academic Press Inc., pp. 65-89.
Convertino, M, Samoshkin, A, Viet, CT, Gauthier, J, Fraine, SPL, Sharif-Naeini, R, Schmidt, BL, Maixner, W, Diatchenko, L & Dokholyan, N 2015, 'Differential regulation of 6- and 7-Transmembrane helix variants of μ-opioid receptor in response to morphine stimulation', PloS one, vol. 10, no. 11, e0142826.
Brown, KA, Zou, Y, Shirvanyants, D, Zhang, J, Samanta, S, Mantravadi, PK, Dokholyan, N & Deiters, A 2015, 'Light-cleavable rapamycin dimer as an optical trigger for protein dimerization', Chemical Communications, vol. 51, no. 26, pp. 5702-5705.
Proctor, EA, Kota, P, Aleksandrov, AA, He, L, Riordan, JR & Dokholyan, N 2015, 'Rational coupled dynamics network manipulation rescues disease-relevant mutant cystic fibrosis transmembrane conductance regulator', Chemical Science, vol. 6, no. 2, pp. 1237-1246.
Convertino, M, Samoshkin, A, Gauthier, J, Gold, MS, Maixner, W, Dokholyan, N & Diatchenko, L 2015, 'μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 62, pp. 61-67.

Clinical Trials Search

Children (age < 18 years)
Adults (age >= 18 years)