title: Gating energetics of a voltage-dependent K+channel pore domain.
abstract: 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. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Swiss Institute of Bioinformatics and Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.|Department of Chemistry, University of California, Irvine, California, 92697-2025.
authors.forename: Greg
authors.initials: G
authors.lastname: Starek
authors.affiliation: Department of Chemistry, University of California, Irvine, California, 92697-2025.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Freites
authors.affiliation: Swiss Institute of Bioinformatics and Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Bernèche
authors.affiliation: Department of Chemistry, University of California, Irvine, California, 92697-2025.
authors.forename: Douglas J
authors.identifier: 0000-0002-6971-9828
authors.initials: DJ
authors.lastname: Tobias
keywords: ion channels; potassium channel; targeted molecular dynamics; umbrella sampling; voltage gating