The Nicotinic Acetylcholine Receptor


(Diagram after F. Hucho, V. Tsetlin and J. Machold, Eur. J. Biochem. 239, 539-557 (1996))

Ion channels are of vital importance in many biological processes, particularly in the nervous system. However, there is much that is unknown about both their structure and their mechanism of operation. In this group we use computer simulation to try to tackle these questions. The figure above is a semi-schematic representation of the Nicotinic Acetylcholine Receptor (nAChR), a cation-selective ion channel found in the nerve-muscle synapse and in neurons. This channel, which is the present focus of my work, is the best-understood member of its family, the ligand-gated ion channels. The nAChR proper consists of 5 similar protein molecules, labelled alpha (2 copies), beta, gamma and delta in the figure. It is shown as it is believed to exist in vivo: inserted into the cell membrane, glycosylated on the extracellular side and associated with a 43 kd peripheral membrane protein that anchors it to the cell's cytoskeleton.

Ion Channels and the nAChR-An Introductory Guide

I still haven't got round to this.

More about Membrane Proteins, the nAChR and Computer Simulation

mostly text

The Nicotinic Receptor in virtual reality

A VRML version of our model of the M2 helix bundle of the nAChR. The water molecules are grey v-shapes, and the protein is space-filling, colour-coded red for negatively charged residues, blue for positively charged, yellow for polar and green otherwise. There is a (purple) Sodium ion in the pore. I find it best to press ^K so you get the 'walk viewer' thing, then you can fly round the model or go plunging into the pore, etc. It seems to take a long time to load (though the file is only 76k; gzipped wrl).

Water in the Nicotinic Receptor

The state of my work in late 1996, as reported in a conference poster. Deals with the physical properties of water and the energetics of sodium ions in a model of the M2 helix bundle.

Dynamic Properties of Ions and Water In Models of Ion Channels

A more up-to-date report on recent work I have been doing to use simulation to measure the diffusion coefficients of ions in models of the nicotinic receptor and other channels, including the fungal peptide alamethicin and an artificial Leucine-Serine peptide (They turn out to be quite substantially reduced). Also contains a bit about the effective dielectric constant of pore water (also reduced).

Publications and Conferences

The papers I have written or contributed to since arriving at the group and the conferences I have attended and, in some cases, spoken at.

Where Do We Go From Here?

possible future developments in our studies of the nAChR and related channels.

What's All This Got To Do With Smoking?

you may well ask...


29/9/96