Figure 9.

(a) Representation of the larger ligand molecules used to study the effect of ligand size on promiscuity. These ligands were composed of eight spheres. The first four were located identically to those in the control ligand. The second four were offset by 4 Å above the others, and by 1.5 Å along the bonding axis. These locations were chosen such that the added spheres would highly desolvate the receptor upon binding, such that large differences in the promiscuity values could be seen. (b) The π₃ values for two sets of ligands toward the same receptor set, plotted against each ligands desolvation energy. One set (red) is composed of “small” ligands, made up of four model atoms. The other set (blue) is composed of larger ligands, of shape shown in (a). This data supports the theoretical prediction that generally, smaller molecules are more promiscuous than large ligands toward the same receptor set. (c) C₋₃ values are shown for each of the smaller (red) and larger (blue) ligands. Few of the larger ligands are able to bind with high affinity to many of the receptors in the panel.