Side-chain conformation at the selectivity filter shapes the permeation free-energy landscape of an ion channel.

ABSTRACT: On the basis of single-channel currents recorded from the muscle nicotinic acetylcholine receptor (AChR), we have recently hypothesized that the conformation adopted by the glutamate side chains at the first turn of the pore-lining α-helices is a key determinant of the rate of ion permeation. In this paper, we set out to test these ideas within a framework of atomic detail and stereochemical rigor by conducting all-atom molecular dynamics and Brownian dynamics simulations on an extensively validated model of the open-channel muscle AChR. Our simulations provided ample support to the notion that the different rotamers of these glutamates partition into two classes that differ markedly in their ability to catalyze ion conduction, and that the conformations of the four wild-type glutamates ar

SUBMITTER: Harpole TJ 

PROVIDER: S-EPMC4128128 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature