Selective ion binding and transport by membrane proteins – A computational perspective

Inorganic ions are critical for cellular function and require an efficient mechanism of transport through the cellular membrane. Most often the transport of ions occurs through proteins known as ion channels and transporters. Ion binding and permeation through these proteins is a complicated process that is still under investigation with a wide range of experimental and theoretical methods. Here we present an overview of some of the competing theories of ion transport with special emphasis on the theoretical methods used for the elucidation of the energetics of ion selectivity, coordination and permeation. A large part of the review is dedicated to potassium and sodium channels and transporters, which are among the best studied biological transport systems and provide a frame of reference for all other ion-protein interactions. In addition, we summarize the computational work done on the transport of several other small inorganic ions (calcium, magnesium, chloride, inorganic phosphate). Our aim is to provide a general picture of the current state of knowledge on biological ion-transport phenomena and to evaluate the capabilities of modern computational methods when applied to ion transport. We also strive to draw attention to some underdeveloped areas of ion transport that require further investigation.