Physics of selective conduction and point mutation in biological ion channels

TL;DR

This paper develops a statistical and linear response theoretical framework to understand selective conduction in biological ion channels, accounting for mutations and Coulomb interactions, and aligns well with experimental data.

Contribution

It introduces a novel theoretical approach combining grand-canonical ensemble and Einstein relations for ion channels with mutations and Coulomb effects.

Findings

Theory matches experimental data from KcsA channels.

Maximum conduction occurs when binding sites are nearly identical.

Eisenman relations emerge from conduction conditions.

Abstract

We introduce a statistical and linear response theory of selective conduction in biological ion channels with multiple binding sites and possible point mutations. We derive an effective grand-canonical ensemble and generalised Einstein relations for the selectivity filter, assuming strongly coordinated ionic motion, and allowing for ionic Coulomb blockade. The theory agrees well with data from the KcsA K$^+$ channel and a mutant. We show that the Eisenman relations for thermodynamic selectivity follow from the condition for fast conduction and find that maximum conduction requires the binding sites to be nearly identical.