The effect of point mutations on energy profiles in a model of the nicotinic acetylcholine receptor (AChR) channel.

Energy profiles are calculated, using energy optimization computations, for a sodium cation in the AChR channel and four of its mutants, alpha E241D, beta E247Q, delta E255Q and alpha E241Q, using the model developed previously. The relative energy location of the calculated profiles confirms and specifies the role of each of the Glu residues found in the anionic ring at the bottom of the MII helices. The structural analysis of the results allows the understanding of the differences observed in the conductances for the wild-type and mutant alpha E241D, or for the mutants beta E247Q and delta E255Q in spite of the identity of the global charge of both channels in each couple. The striking correlation observed between the average relative energy location of the profiles and the conductance data appears to provide confirmation of the essential structural features adopted in the model, in particular the inclusion of the Glu(Gln in gamma)-Lys residues in the alpha-helical stretch of the MII helices and the overall location of the internal residues.