Molecular mechanics of the formation of cholic acid micelles

The molecular mechanics of cholic acid micelle formation were simulated using the Sybyl energy minimization program (MAXIMIN2), developed by Tripos Associates, interfaced with micro-Vax. Before energy minimization, the molecular dimensions of the cholic acid dodecamer C24H40O6, in terms of the unit cell axes a, b, and c in the cubic crystal class, had values of 13, 18, and 6.7 A, respectively. After energy minimization, at 9370 kcals/dodecamer, these values had increased to 21.6, 42.8 and 20.9 A. At an energy minimization level of 21,626 kcals/dodecamer, the micelle structure is stabilized by hydrophobic interaction, forming distinct horizontal channels along the b-axis, directing the carboxyl and hydroxyl groups toward the surface. These structural changes remain relatively constant as the process of energy minimization continues, down to the lowest energy level we considered, 9370 kcals/dodecamer. The cholic acid layers are highly dissimilar, forming channels of irregular size and shape in a somewhat helical structure. The carboxyl groups and phenanthrene rings are in a puckered orientation, which permits compact packing of the sandwiched multilayers. From the dimension of the channels, it is apparent that guest molecules, such as phospholipid, cholesterol, or inorganic calcium, can be incorporated into the micelle through more than one channel, forming inclusion complexes, such as gallstones.