Lei Shi, Ph.D.


Molecular Targets and Medications Discovery Branch, Computational Chemistry and Molecular Biophysics Unit


Triad Technology Center
333 Cassell Drive
Room 1121
Baltimore, MD 21224



Research Topics

Membrane proteins (MP) initiate intracellular signaling pathways, control the flow of energy and materials in and out of the cell, and thereby account for more than 30% of the entire proteome and 40% of drug targets. Research interests in the lab are focused on identifying common and specific structural basis of MP functions to advance the mechanistic understanding of key cellular processes, from the disparate yet intertwined perspectives of functional mechanisms and molecular recognition. Using a combined approach of computational and experimental analysis, we are interested in elucidating the atomistic details of allosteric conformational transitions and propagations during signal transduction and transport processes. In particular, we investigate the critical structural and dynamic elements that determine ligand binding specificities, the interactions among MP and their coupled proteins, and the associations of MP with the lipid bilayer. The findings allow us to rationally optimize existing and develop new compounds that shift the conformational equilibrium of MP, which will facilitate functional studies and lead to novel drug discovery.

Selected Publications

  1. Abramyan AM, Slack RD, Meena S, Davis BA, Newman AH, Singh SK, Shi L. Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics. Neuropharmacology. 2018.

  2. Verma RK, Abramyan AM, Michino M, Free RB, Sibley DR, Javitch JA, Lane JR, Shi L. The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors. PLoS Comput Biol. 2018;14(1):e1005948.

  3. Abramyan AM, Stolzenberg S, Li Z, Loland CJ, Noé F, Shi L. The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes to Its Selection of the Transporter Conformation. ACS Chem Neurosci. 2017;8(8):1735-1746.

  4. Michino M, Boateng CA, Donthamsetti P, Yano H, Bakare OM, Bonifazi A, Ellenberger MP, Keck TM, Kumar V, Zhu C, Verma R, Deschamps JR, Javitch JA, Newman AH, Shi L. Toward Understanding the Structural Basis of Partial Agonism at the Dopamine D<sub>3</sub> Receptor. J Med Chem. 2017;60(2):580-593.

  5. Stolzenberg S, Quick M, Zhao C, Gotfryd K, Khelashvili G, Gether U, Loland CJ, Javitch JA, Noskov S, Weinstein H, Shi L. Mechanism of the Association between Na+ Binding and Conformations at the Intracellular Gate in Neurotransmitter:Sodium Symporters. J Biol Chem. 2015;290(22):13992-4003.

This page was last updated on November 2nd, 2018