Role of Water Models in Simulations of Ion Conduction in Potassium Channels
Stefano Bosio, Diego Gazzoni, Carmen Domene, Matteo Masetti, Simone Furini
TL;DR
This paper investigates how different water models affect simulations of ion conduction in potassium channels, revealing that both hard and soft knock-on mechanisms can coexist and transition reversibly.
Contribution
The study demonstrates that simulation parameters, particularly water models, significantly influence observed ion conduction mechanisms in potassium channels.
Findings
Both hard and soft knock-on mechanisms are accessible and can reversibly transition in MthK and KcsA channels.
The OPC water model allows coexistence of both mechanisms, unlike the TIP3P model which favors hard knock-on.
Simulation parameters critically influence potassium channel permeation behavior and reconcile conflicting experimental observations.
Abstract
Potassium channels exhibit high selectivity and conductance, yet the atomic details of ion permeation, particularly the involvement of water molecules, remain debated. Two main conduction mechanisms have been proposed: the hard knock-on, in which ions traverse the selectivity filter in direct contact, and the soft knock-on, which involves copermeation of water molecules. Using microsecond molecular dynamics simulations with the OPC water model, the AMBER19SB protein force field, and the 12–6–4 Sengupta et al. ion model, and an analysis strategy based on Markov State Models, we observed that both hard and soft knock-on mechanisms are accessible and, notably, can reversibly transition in the MthK and KcsA channels across all simulated membrane potentials. These reversible transitions contrast with previous observations using the TIP3P water model, where water entry either disrupted…
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Taxonomy
TopicsIon channel regulation and function · Ion Channels and Receptors · Nanopore and Nanochannel Transport Studies