Many-body effects and simulations of potassium channels

Abstract

The electronic polarizability of an ion or a molecule is a measure of the relative tendency of its electron cloud to be distorted from its normal shape by an electric field. On the molecular scale, in a condensed phase, any species sits in an electric field due to its neighbours, and the resulting polarization is an important contribution to the total interaction energy. Electrostatic interactions are crucial for determining the majority of chemical-physical properties of the system and electronic polarization is a fundamental component of these interactions. Thus, polarization effects should be taken into account if accurate descriptions are desired. In classical computer simulations, the forces required to drive the system are typically based on interatomic interaction potentials derived in part from electronic structure calculations or from experimental data. Owing to the difficulties in including polarization effects in classical force fields, most of them are based just on pairwise additive interaction potentials. At present, major efforts are underway to develop polarizable interaction potentials for biomolecular simulations. In this review, various ways of introducing explicit polarizability into biomolecular models and force fields are reviewed, and the progress that might be achieved in applying such methods to study potassium channels is described.

Selectivity and Permeation of Alkali Metal Ions in K+-channels

“…It is likely that electronic polarization plays an effect during the movement of the ions and water through the ion channel, especially in the case of Rb + , and this merits further study. 25,32 In the absence of a fully developed polarizable force field for water, ions, protein and lipids, the current study represents an attempt to delineate some of the main features of ion permeability and selectivity in a typical K + -channel.…”

Analysis of the selectivity filter of the voltage-gated sodium channel NavRh

“…There are limitations in our MD simulations. First, the non-polarizable force field was adopted here to accelerate computation, which may introduce errors since the non-negligible charge transfer from protein to the bound cation is omitted in non-polarizable force field [49]. Second, the current CHARMM force field cannot perfectly reproduce the solvation energy of Ca 2+ ions.…”

Voltage-Gated Sodium Channels

“…Therefore, the continued improvement of polarizable forcefields will enhance the accuracy to which ion permeation can be simulated (Illingworth & Domene, 2009;Vanommeslaeghe & MacKerell Jr, 2015;Xu et al, 2015).…”