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.

Effect of Intercalated Water on Potassium Ion Transport through Kv1.2 Channels Studied via On-the-Fly Free-Energy Parametrization / Paz, S. A.; Maragliano, L.; Abrams, C. F.. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - 14:5(2018), pp. 2743-2750. [10.1021/acs.jctc.8b00024]

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

Maragliano L.;
2018-01-01

Abstract

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.
2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/276705
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