The acetylcholine molecule (See Figure 4.1) has been widely studied due to its central rôle in neural transmission. This makes it an ideal candidate for an investigation to validate the computational methods described in Chapter 2 for use in modeling the energetics of bio-organic molecules. A number of semi-empirical computational studies have been performed on this molecule with the aim of ascertaining its most stable conformation [12] [13] [14] [15]. Comparison of the results obtained with experimental results will allow conclusions to be drawn regarding the use of these ab initio techniques in place of semi-empirical methods.
Figure 4.1: A computer generated representation of the acetylcholine
molecule. (C=Grey, O=Red, N=Blue, H=Yellow)
The conformation of acetylcholine may be described by the dihedral
angles D1 through D4 as indicated in Figure 4.2. The
conformational energy map as a function of the two central dihedral
angles D2 and D3 has been investigated. The dihedral angle of the
four bonded atoms A--B--C--D, 
is defined by the angle
between the planes ABC and BCD viewed from the side of A, such that a
positive angle is given by clockwise rotation of the far end with
respect to the near and an angle of 0 corresponds to the
cis-planar arrangement of the bonds AB and CD.
Figure 4.2: The chemical structure of acetylcholine defining dihedral
angles D1 through D4.
The initial structural data was obtained from a crystallographic study of acetylcholine chloride [16].
This investigation was presented in the form of a poster at the UK Association of Pharmaceutical Scientists' Annual Conference in Nottingham between 11 April and 13 April 1995.