Guardiani, Carlo, Rodger, P. Mark, Fedorenko, Olena A., Roberts, Stephen K. and Khovanov, Igor A. (2017) Data for Sodium binding sites and permeation mechanism in the NaChBac channel: a Molecular Dynamics study. [Dataset]

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Abstract

NaChBac was the first discovered bacterial sodium voltage-dependent channel, yet computational studies are still limited due to the lack of a crystal structure. In this work, a pore-only construct built using the NavMs template was investigated using unbiased molecular dynamics and metadynamics. The potential of mean force (PMF) from the unbiased run features four minima, three of which correspond to sites IN, CEN, and HFS discovered in NavAb. During the run, the selectivity filter (SF) is spontaneously occupied by two ions, and frequent access of a third one is often observed. In the innermost sites IN and CEN, Na+ is fully hydrated by six water molecules and occupies an on-axis position. In site HFS sodium interacts with a glutamate and a serine from the same subunit and is forced to adopt an off-axis placement. Metadynamics simulations biasing one and two ions show an energy barrier in the SF that prevents single-ion permeation. An analysis of the permeation mechanism was performed both computing minimum energy paths in the axial–axial PMF and through a combination of Markov state modeling and transition path theory. Both approaches reveal a knock-on mechanism involving at least two but possibly three ions. The currents predicted from the unbiased simulation using linear response theory are in excellent agreement with single-channel patch-clamp recordings.

Item Type:	Dataset
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH):	Sodium channels, Potassium channels, Cations, Molecular Dynamics
Publisher:	University of Warwick, School of Engineering
Official Date:	13 January 2017
Dates:	Date Event 13 January 2017 Accepted
Status:	Not Peer Reviewed
Media of Output (format):	.txt
Description:	Homology model of NaChBac channel pore domain
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID EP/M016889/1 [EPSRC] Engineering and Physical Sciences Research Council http://dx.doi.org/10.13039/501100000266 EP/M015831/1 [EPSRC] Engineering and Physical Sciences Research Council http://dx.doi.org/10.13039/501100000266 EP/K000128/1 [EPSRC] Engineering and Physical Sciences Research Council http://dx.doi.org/10.13039/501100000266
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