Exploring the Viral Channel KcvPBCV-1 Function via Computation

Abstract

Viral potassium channels (Kcv) are homologous to the pore module of complex -selective ion channels of cellular organisms. Due to their relative simplicity, they have attracted interest towards understanding the principles of conduction and channel gating. In this work, we construct a homology model of the open state, which we validate by studying the binding of known blockers and by monitoring ion conduction through the channel. Molecular dynamics simulations of this model reveal that the re-orientation of selectivity filter carbonyl groups coincides with the transport of potassium ions, suggesting a possible mechanism for fast gating. In addition, we show that the voltage sensitivity of this mechanism can originate from the relocation of potassium ions inside the selectivity filter. We also explore the interaction of with the surrounding bilayer and observe the binding of lipids in the area between two adjacent subunits. The model is available to the scientific community to further explore the structure/function relationship of Kcv channels.Electronic supplementary materialThe online version of this article (doi:10.1007/s00232-018-0022-2) contains supplementary material, which is available to authorized users.

Gating movements and ion permeation in HCN4 pacemaker channels

“…Short trial simulations were also performed to test a range of applied voltages and ion solution concentrations. To increase the rate of sampling of conduction events during production runs, we applied artificial electric fields of −500mV or −700mV ( Andersson et al., 2018 ; Köpfer et al., 2014 ; Stock et al., 2013 ). However, the same conduction mechanism was observed at hyperpolarizing voltages as low as −300mV and ion concentrations as low as 150 mV.…”

A small viral potassium ion channel with an inherent inward rectification

“…Hence the selectivity filter or the fine-tuning of the filter geometry seems to be irrelevant for an inherent inward rectification. This finding is unexpected considering the fact that inherent rectification is voltage and K + sensitive and that the filter is the domain, which provides the selectivity [1] for the channel and where the majority of the voltage drop in a K + channel occurs [39,40].…”

A small viral potassium ion channel with an inherent inward rectification

“…Hence the selectivity filter or the fine-tuning of the filter geometry seems to be irrelevant for an inherent inward rectification. This finding is unexpected considering the fact that inherent rectification is voltage and K + sensitive and that the filter is the domain, which provides the selectivity (Doyle et al, 1998) for the channel and where the majority of the voltage drop in a K + channel occurs (Contreras, et al, 2010;Andersson et al, 2018).…”