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

By S. Alexis Paz (1512865), Luca Maragliano (523114) and Cameron F. Abrams (1321032)


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<sup>+</sup> 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 <i>knock-on</i> 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

Topics: Biophysics, Biochemistry, Physiology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, On-the-Fly Free-Energy Parametrization, ions translocation, OTFP -2D algorithm, free-energy surfaces, Potassium Ion Transport, name OTFP -2D, 2 D free-energy surfaces, solvated alanine dipeptide, Kv 1.2 Channels Studied, Molecular Dynamics simulations, water molecules, energy parametrization, intercalated water molecules, dihedral angles, Intercalated Water, sampling acceleration, method, Kv 1.2 channel, ion movement, knock-on mechanism, energy surface, biomacromolecular simulations, energy surfaces, ion translocation
Year: 2018
DOI identifier: 10.1021/acs.jctc.8b00024.s001
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