The solute-solvent system: Solvent constraints on the conformational dynamics of acetylcholine

The objective of this study was to determine if and how a solvent influences internal motions in a solute molecule. Acetylcholine was chosen as the object of study given its interesting molecular structure and major biological significance. Molecular dynamics simulations were carried out in the vacuum (10 ns), water (5 ns), methanol (5 ns), and octanol (1.5 ns). Seven clusters of conformers were identified, namely, +g+g, -g-g, +gt, -gt, t+g, t-g, and tt, where the gauche and trans labels refer to the dihedral angles tau(2) and tau(3), respectively. As expected, the relative proportion of these conformational clusters was highly solvent-dependent and corresponded to a progressive loss of conformational freedom with increasing molecular weight of the solvent. More importantly, the conformational clusters were used to calculate instantaneous and median angular velocity (omega and omega(M), respectively) and instantaneous and median angular acceleration (a and am, respectively). Angular velocity and angular acceleration were both found to decrease markedly with increasing molecular weight of the solvent, i.e., vacuum (epsilon = 1) > water > methanol > octanol. The decrease from the vacuum to octanol was similar to40% for tau(2) and similar to60% for tau(3). Such solvent-dependent constraints on a solute's internal motions may be biologically and pharmacologically relevant.