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Effect of Intercalated Water on Potassium Ion Transport through Kv1.2 Channels Studied via On-the-Fly Free-Energy Parametrization
Journal article   Open access   Peer reviewed

Effect of Intercalated Water on Potassium Ion Transport through Kv1.2 Channels Studied via On-the-Fly Free-Energy Parametrization

S Alexis Paz, Luca Maragliano and Cameron F Abrams
Journal of chemical theory and computation, v 14(5), pp 2743-2750
08 May 2018
PMID: 29570282
url
https://doi.org/10.1021/acs.jctc.8b00024View
Published, Version of Record (VoR) Open

Abstract

Water - chemistry Alanine - chemistry Ion Transport Dipeptides - chemistry Molecular Dynamics Simulation Kv1.2 Potassium Channel - chemistry Potassium - chemistry
We introduce a two-dimensional version of the method called on-the-fly free energy parametrization (OTFP) to reconstruct free-energy surfaces using Molecular Dynamics simulations, which we name OTFP-2D. We first test the new method by reconstructing the well-known dihedral angles free energy surface of solvated alanine dipeptide. Then, we use it to investigate the process of K ions translocation inside the Kv1.2 channel. By comparing a series of two-dimensional free energy surfaces for ion movement calculated with different conditions on the intercalated water molecules, we first recapitulate the widely accepted knock-on mechanism for ion translocation and then confirm that permeation occurs with water molecules alternated among the ions, in accordance with the latest experimental findings. From a methodological standpoint, our new OTFP-2D algorithm demonstrates the excellent sampling acceleration of temperature-accelerated molecular dynamics and the ability to efficiently compute 2D free-energy surfaces. It will therefore be useful in large variety complex biomacromolecular simulations.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Chemistry, Physical
Physics, Atomic, Molecular & Chemical
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