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