Nikolay Dokholyan

Professor, Department of Neurology

dokh@virginia.edu

Phone (434) 429-0976

Lab website https://dokhlab.org

Research Disciplines

Molecular neuroscience, biophysics, biochemistry, machine learning/artificial intelligence, drug discovery, molecular engineering, neurodegeneration, translational research

Research Interests 

Early events in neurodegeneration, engineering of cellular nanocomputing agents, cell reprogramming, machine learning, artificial intelligence

Research Description 

The Dokholyan laboratory is engaged in translational research with a focus on neurodegeneration and cancer. Dokholyan laboratory utilizes several integrated computational and experimental strategies to understand, sense (recognize and report), and control aberrant biological molecules, and uncover etiologies of human diseases, such as amyotrophic lateral sclerosis(ALS), Alzheimer’s, and Parkinson’s diseases. For the past two decades, the Dokholyan laboratory has been developing approaches to molecular structural modeling and dynamic simulations, allowing the study of the structure and dynamics of biological molecules at time scales relevant to biological systems. These approaches uniquely integrate rapid physical dynamics simulations, experiments, and molecular modeling and design, allowing us to make significant breakthroughs in understanding etiologies of cystic fibrosis and ALS. Such integration allows the Dokholyan laboratory to perform translational research: from understanding molecular players at the atomic level to probing their function at the cellular and organismal level, as well as discovering molecular therapeutic strategies to affect these players.

Selected Publications

D. Khare, M. Caplow, and N. V. Dokholyan, "The rate and equilibrium constants for a multi-step reaction sequence for the aggregation of superoxide dismutase in Amyotrophic Lateral Sclerosis" PNAS, 101: 15094-15099 (2004)

F. Ding, S. Yin, and N. V. Dokholyan, "Rapid flexible docking using a stochastic rotamer library of ligands" Journal of Chemical Information and Modeling, 50: 1623-1632 (2010) PMCID: PMC2947618

F. Ding, C. A. Lavender, K. M. Weeks, and N. V. Dokholyan, "Three-dimensional RNA structure refinement by hydroxyl radical probing" Nature Methods, 9: 603-608 (2012)

Proctor, E. A., Fee, L., Tao, Y., Redler, R. L., Fay, J. M., Zhang, Y., Lv, Z., Mercer, I. P., Deshmukh, M., Lyubchenko, Y. L., and Dokholyan, N. V. "Non-native SOD1 trimer is toxic to motor neurons in a model of amyotrophic lateral sclerosis", PNAS, 113:614-619 (2016) PMCID: PMC4725519

O. Dagliyan, M. Tarnawski, P. H. Chu, D. Shirvanyants, I. Schlichting, N. V. Dokholyan*, K. M. Hahn*, “Engineering extrinsic disorder to control protein activity in living cells”, Science 354: 1441-1444 (2016) PMCID: PMC5362825

O. Dagliyan, A. Krokhotin, I. Ozkan-Dagliyan, A. Deiters, C. J. Der, K. M. Hahn, & N. V. Dokholyan, “Computational design of chemogenetic and optogenetic split proteins” Nature Communications, 9: 4042 (2018)