![Lei Shi, Ph.D.](https://irp.nida.nih.gov/wp-content/uploads/2017/11/Lei-Shi-223x300.jpg)
Contact
Triad Technology Center333 Cassell Drive
Room 1121
Baltimore, MD 21224
Phone: 667-312-5284
Email: [email protected]
Education
Post-doctoral Training - Center for Molecular Recognition, Columbia University Medical Center (advisor: Dr. Jonathan A. Javitch); Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Cornell Medical College (advisor: Dr. Harel Weinstein)
Ph.D. - Pharmacology, Columbia University Medical Center (advisor: Dr. Jonathan A. Javitch)
B.S. - Biochemistry and Molecular Biology, Beijing University
Research Interests
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 human proteome and 40% of drug targets. Research interest in the lab is focused on investigating structural basis of MP functions to advance mechanistic understanding of key cellular processes. Using a combined computational and experimental approach, we identify and characterize the elements that determine the recognitions between MP and their cognate ligands, between MP and their coupled proteins, and between MP and lipid environment. The integrated findings allow us to rationally develop small-molecule compounds for novel drug discovery.
Publications
Selected Publications
Research
GPCR-mediated β-arrestin activation deconvoluted with single-molecule precision Journal Article In: Cell, 2022, ISSN: 1097-4172. Toward Reducing hERG Affinities for DAT Inhibitors with a Combined Machine Learning and Molecular Modeling Approach Journal Article In: J Chem Inf Model, vol. 61, no. 9, pp. 4266–4279, 2021, ISSN: 1549-960X. The mechanism of a high-affinity allosteric inhibitor of the serotonin transporter Journal Article In: Nature Communications, vol. 11, no. 1, pp. 1491, 2020, ISBN: 2041-1723. Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism Journal Article In: eLife, vol. 9, pp. e52189, 2020, ISSN: 2050-084X. Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics Journal Article In: Neuropharmacology, vol. 161, pp. 107411, 2019, ISSN: 0028-3908, (Neurotransmitter Transporters). The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors Journal Article In: PLoS Comput Biol, vol. 14, no. 1, pp. e1005948, 2018, ISSN: 1553-7358 (Electronic) 1553-734X (Linking). Pharmacological profiling of sigma 1 receptor ligands by novel receptor homomer assays Journal Article In: Neuropharmacology, vol. 133, pp. 264-275, 2018, ISSN: 1873-7064 (Electronic) 0028-3908 (Linking). The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes to Its Selection of the Transporter Conformation Journal Article In: ACS Chem Neurosci, vol. 8, no. 8, pp. 1735-1746, 2017, ISSN: 1948-7193 (Electronic) 1948-7193 (Linking). Toward Understanding the Structural Basis of Partial Agonism at the Dopamine D3 Receptor Journal Article In: J Med Chem, vol. 60, no. 2, pp. 580-593, 2017, ISSN: 1520-4804 (Electronic) 0022-2623 (Linking). In: J Biol Chem, vol. 292, no. 18, pp. 7372-7384, 2017, ISSN: 1083-351X (Electronic) 0021-9258 (Linking). Computational approaches to detect allosteric pathways in transmembrane molecular machines Journal Article In: Biochim Biophys Acta, vol. 1858, no. 7 Pt B, pp. 1652-62, 2016, ISSN: 0006-3002 (Print) 0006-3002 (Linking).2022
2021
2020
2019
2018
2017
2016
Review
A new era of rationally designed antipsychotics Journal Article In: Nature, vol. 555, no. 7695, pp. 170-172, 2018, ISSN: 1476-4687 (Electronic) 0028-0836 (Linking). Editorial: Computer Aided Structure-based Lead Optimization Journal Article In: Curr Top Med Chem, vol. 17, no. 23, pp. 2575-2576, 2017, ISSN: 1873-4294 (Electronic) 1568-0266 (Linking). What can crystal structures of aminergic receptors tell us about designing subtype-selective ligands? Journal Article In: Pharmacol Rev, vol. 67, no. 1, pp. 198–213, 2015, ISSN: 1521-0081 (Electronic); 0031-6997 (Linking).2018
2017
2015
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