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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 contribution
posted on 2018-03-23, 00:00 authored by S. Alexis Paz, Luca Maragliano, Cameron F. AbramsWe 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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On-the-Fly Free-Energy Parametrizationions translocationOTFP -2D algorithmfree-energy surfacesPotassium Ion Transportname OTFP -2D2 D free-energy surfacessolvated alanine dipeptideKv 1.2 Channels StudiedMolecular Dynamics simulationswater moleculesenergy parametrizationintercalated water moleculesdihedral anglesIntercalated Watersampling accelerationmethodKv 1.2 channelion movementknock-on mechanismenergy surfacebiomacromolecular simulationsenergy surfacesion translocation
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