From Structure to Function in Open Ionic Channels

TL;DR

This paper explores whether the permeation properties of open ionic channels can be predicted solely through mean field electrostatics and electrodiffusion, minimizing the need for complex chemical explanations.

Contribution

It proposes a hypothesis that ionic channel functions can be understood mainly through electrodiffusion in fixed structures, reducing reliance on conformational or chemical change models.

Findings

Many properties of open ionic channels can be explained by mean field electrostatics.

Electrodiffusion laws applied to channel structures predict permeation behaviors.

Chemical-specific explanations are needed only when mean field models fail.

Abstract

We consider a simple working hypothesis that all permeation properties of open ionic channels can be predicted by understanding electrodiffusion in fixed structures, without invoking conformation changes, or changes in chemical bonds. We know, of course, that ions can bind to specific protein structures, and that this binding is not easily described by the traditional electrostatic equations of physics textbooks, that describe average electric fields, the so-called `mean field'. The question is which specific properties can be explained just by mean field electrostatics and which cannot. I believe the best way to uncover the specific chemical properties of channels is to invoke them as little as possible, seeking to explain with mean field electrostatics first. Then, when phenomena appear that cannot be described that way, by the mean field alone, we turn to chemically specific explanations, seeking the appropriate tools (of electrochemistry, Langevin, or molecular dynamics, for example) to understand them. In this spirit, we turn now to the structure of open ionic channels, apply the laws of electrodiffusion to them, and see how many of their properties we can predict just that way.