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Open AccessArticle

Formation Mechanism of Ion Channel in Channelrhodopsin-2: Molecular Dynamics Simulation and Steering Molecular Dynamics Simulations

1
Chongqing Key Laboratory of Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 40065, China
2
Department of Chemistry and Physical Sciences, Nicholls State University, P.O. Box 2022, Thibodaux, LA 70310, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3780; https://doi.org/10.3390/ijms20153780
Received: 15 July 2019 / Accepted: 30 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Ion Channel and Ion-Related Signaling 2019)
Channelrhodopsin-2 (ChR2) is a light-activated and non-selective cationic channel protein that can be easily expressed in specific neurons to control neuronal activity by light. Although ChR2 has been extensively used as an optogenetic tool in neuroscience research, the molecular mechanism of cation channel formation following retinal photoisomerization in ChR2 is not well understood. In this paper, studies of the closed and opened state ChR2 structures are presented. The formation of the cationic channel is elucidated in atomic detail using molecular dynamics simulations on the all-trans-retinal (ChR2-trans) configuration of ChR2 and its isomerization products, 13-cis-retinal (ChR2-cis) configuration, respectively. Photoisomerization of the retinal-chromophore causes the destruction of interactions among the crucial residues (e.g., E90, E82, N258, and R268) around the channel and the extended H-bond network mediated by numerous water molecules, which opens the pore. Steering molecular dynamics (SMD) simulations show that the electrostatic interactions at the binding sites in intracellular gate (ICG) and central gate (CG) can influence the transmembrane transport of Na+ in ChR2-cis obviously. Potential of mean force (PMF) constructed by SMD and umbrella sampling also found the existing energy wells at these two binding sites during the transportation of Na+. These wells partly hinder the penetration of Na+ into cytoplasm through the ion channel. This investigation provides a theoretical insight on the formation mechanism of ion channels and the mechanism of ion permeation. View Full-Text
Keywords: channelrhodopsin-2; photoisomerization; ion channel; hydrogen bond network; Steering Molecular Dynamics Simulations channelrhodopsin-2; photoisomerization; ion channel; hydrogen bond network; Steering Molecular Dynamics Simulations
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Yang, T.; Zhang, W.; Cheng, J.; Nie, Y.; Xin, Q.; Yuan, S.; Dou, Y. Formation Mechanism of Ion Channel in Channelrhodopsin-2: Molecular Dynamics Simulation and Steering Molecular Dynamics Simulations. Int. J. Mol. Sci. 2019, 20, 3780.

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