Incidence of partial charges on ion selectivity in potassium channels

Abstract

Potassium channels are membrane proteins known to select potassium over sodium ions at a high diffusion rate. We conducted ab initio calculations on a filter model of KcsA of about 300 atoms at the Hartree-Fock level of theory. Partial charges were derived from the quantum mechanically determined electrostatic potential either with Merz-Kollman or Hinsen-Roux schemes. Large polarization and/or charge transfer occur on potassium ions located in the filter, while the charges on sodium ions remain closer to unity. As a result, a weaker binding is obtained for K(+) ions. Using a simplified version of a permeation model based on the concerted-motion mechanism for ion translocation within the single-file ion channel [P. H. Nelson, J. Chem. Phys. 117, 11396 (2002)], we discuss how differences in polarization effects in the adducts with K(+) and Na(+) can play a role as for ionic selectivity and conductance.

Modeling hERG and its Interactions with Drugs: Recent Advances in Light of Current Potassium Channel Simulations

“…Several dif- www.chemmedchem.org ferent computational approaches have been applied, that is, mainly molecular dynamics [19][20][21] (MD), but also Brownian dynamics, [22] and Monte Carlo simulations [23] to study the conformational behavior of the filter, and free energy perturbation [24,25] (FEP), potential of mean force [26,27] (PMF), and quantum mechanical (QM) calculations [28,29] to capture free energy and electronic aspects of ion conduction and selectivity. From these studies, a coherent picture of the selectivity filter occupancy emerges consisting of a single line of two K + ions (plus one at the external mouth) separated by two water molecules located in the five S 0 (external) through S 4 crystallographic sites ( Figure 3).…”

Molecular dynamics simulations of potassium channels

“…Nevertheless, it is expected to see future research directed at quantum mechanics/molecular mechanics (QM/MM) and ab initio simulation methods, with the advent of linear-scaling quantum mechanical methods. Some of these ab initio techniques have already been applied in K-channel studies [50][51][52][53][54][55]. These studies have focused on studying the physical origins of the barrier-less knock-on diffussion mechanism taking into account ion polarization [54] and calculation of electrostatic potentials and binding energies and the influence of polarization effects [51].…”

Inverted Mexican Hat potential in activation of receptor cells

“…If the processing (activation or inhibition) is performed at the typical size of a bipolar cell, then this means a few micrometer scale L = 2 ÷ 5 µm. However, the opening and closing of ionic channels may take place at the scale of ionic channels [14][15][16][17], and this may be two orders less in size, i.e. about 3 nm.…”