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19 results on '"Shen, Juwen"'

12. Valency-Controlled Framework Nucleic Acid Signal Amplifiers

Author

Liu, Qi, primary, Ge, Zhilei, additional, Mao, Xiuhai, additional, Zhou, Guobao, additional, Zuo, Xiaolei, additional, Shen, Juwen, additional, Shi, Jiye, additional, Li, Jiang, additional, Wang, Lihua, additional, Chen, Xiaoqing, additional, and Fan, Chunhai, additional

Published
2018
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18. General Pharmacological Activation Mechanism of K+Channels Bypassing Channel Gates

Author

Liu, Shijie, Guo, Peipei, Wang, Kun, Zhang, Shaoying, Li, Ya, Shen, Juwen, Mei, Lianghe, Ye, Yangliang, Zhang, Qiansen, and Yang, Huaiyu

Abstract

Under the known pharmacological activation mechanisms, activators allosterically or directly open potassium channel gates. However, herein, molecular dynamics simulations on TREK-1, a member of the channel class gated at the filter, suggested that negatively charged activators act with a gate-independent mechanism where compounds increase currents by promoting ions passing through the central cavity. Then, based on studies of KCNQ2, we uncovered that this noncanonical activation mechanism is shared by the other channel class gated at the helix-bundle crossing. Rational drug design found a novel KCNQ2 agonist, CLE030, which stably binds to the central cavity. Functional analysis, molecular dynamics simulations, and calculations of the potential of mean force revealed that the carbonyl oxygen of CLE030 influences permeant ions in the central cavity to contribute to its activation effects. Together, this study discovered a ligand-to-ion activation mechanism for channels that bypasses their gates and thus is conserved across subfamilies with different gates.

Published
2022
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19. General Pharmacological Activation Mechanism of K + Channels Bypassing Channel Gates.

Author

Liu S, Guo P, Wang K, Zhang S, Li Y, Shen J, Mei L, Ye Y, Zhang Q, and Yang H

Subjects
Ions pharmacology, Ion Channel Gating, Molecular Dynamics Simulation
Abstract

Under the known pharmacological activation mechanisms, activators allosterically or directly open potassium channel gates. However, herein, molecular dynamics simulations on TREK-1, a member of the channel class gated at the filter, suggested that negatively charged activators act with a gate-independent mechanism where compounds increase currents by promoting ions passing through the central cavity. Then, based on studies of KCNQ2, we uncovered that this noncanonical activation mechanism is shared by the other channel class gated at the helix-bundle crossing. Rational drug design found a novel KCNQ2 agonist, CLE030, which stably binds to the central cavity. Functional analysis, molecular dynamics simulations, and calculations of the potential of mean force revealed that the carbonyl oxygen of CLE030 influences permeant ions in the central cavity to contribute to its activation effects. Together, this study discovered a ligand-to-ion activation mechanism for channels that bypasses their gates and thus is conserved across subfamilies with different gates.

Published
2022
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