Gating energetics of a voltage-dependent K+ channel pore domain

被引：4

作者：

Starek, Greg ^{[1
,2
,3
]}

Freites, J. Alfredo ^{[3
]}

Berneche, Simon ^{[1
,2
]}

Tobias, Douglas J. ^{[3
]}

机构：

[1] Univ Basel, Swiss Inst Bioinformat, Klingelbergstr 50-70, CH-4056 Basel, Switzerland

[2] Univ Basel, Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland

[3] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

来源：

JOURNAL OF COMPUTATIONAL CHEMISTRY | 2017年 / 38卷 / 16期

关键词：

ion channels; voltage gating; potassium channel; targeted molecular dynamics; umbrella sampling; MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; POTASSIUM CHANNELS; ION CHANNELS; TRANSMEMBRANE MOVEMENT; ACTIVATION GATE; RESTING STATE; FORCE-FIELD; CHARMM; SENSOR;

D O I：

10.1002/jcc.24742

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We used targeted molecular dynamics, informed by experimentally determined inter-atomic distances defining the pore region of open and closed states of the KvAP voltage-gated potassium channel, to generate a gating pathway of the pore domain in the absence of the voltage-sensing domains. We then performed umbrella sampling simulations along this pathway to calculate a potential of mean force that describes the free energy landscape connecting the closed and open conformations of the pore domain. The resulting energetic landscape displays three minima, corresponding to stable open, closed, and intermediate conformations with roughly similar stabilities. We found that the extent of hydration of the interior of the pore domain could influence the free energy landscape for pore opening/closing. (c) 2017 Wiley Periodicals, Inc.

引用

页码：1472 / 1478

页数：7

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