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You are here: Home Administration Chemistry & Biochemistry Department Events 2019 Fall Semester Biochemistry Seminar: Jana Shen, "Mechanisms of Proton-Coupled Dynamics: From Kinases to Membrane Transporters"

Biochemistry Seminar: Jana Shen, "Mechanisms of Proton-Coupled Dynamics: From Kinases to Membrane Transporters"

Jana Shen, Associate Professor, Fischell Department of Bioengineering, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, MD, "Mechanisms of Proton-Coupled Dynamics: From Kinases to Membrane Transporters"
When Oct 16, 2019
from 12:00 PM to 01:00 PM
Where CUNY ASRC Main Auditorium
Contact Name
Contact Phone 212-650-8803
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Proton-coupled dynamics is ubiquitous in biology; however, detailed mechanisms remain elusive. In this talk, I will introduce a computer simulation tool called continuous constant pH molecular dynamics (CpHMD) and discuss its applications to advance the understanding of protein kinases and membrane transporters. Kinases are cellular signaling molecules involved in cancer and many other diseases. CpHMD was used to reveal the nucleophilic hotspots [1] and activation conformational landscape [2]. Our work suggested a new strategy for targeted covalent inhibitor design and a paradigm shift in the mechanistic understanding of kinases. In the second part of the talk, I will discuss the CpHMD simulations that resolved the proton binding sites in the E. coli multi-drug efflux pump AcrB [3] and the activation mechanism of the E. coli proton-sodium antiporter NhaA [4]. These studies demonstrated the versatile utility of proton-coupled dynamical simulations to offer novel insights into secondary active transporters that play significant roles in human health and disease conditions but remain challenging to study experimentally.

[1] Liu R, Yue Z, Tsai CC, and Shen J, Assessing lysine and cysteine reactivities for designing targeted covalent kinase inhibitors. J Am Chem Soc 141: 6553-6560, 2019.
[2] Tsai CC, Yue Z, and Shen J, How electrostatic coupling enables conformational plasticity in a tyrosine kinase. J Am Chem Soc, ASAP, 2019.
[3] Yue Z, Chen W, Zgurskaya, H, and Shen J*, Constant pH molecular dynamics reveals how proton release drives the conformational transition of a transmembrane efflux pump. J Chem Theory Comput 13: 6405-6414, 2017.
[4] Huang YD, Chen W, Dotson DL, Beckstein O, and Shen J*, Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA. Nat Commun 7: 12940, 2016.

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