Figure 6.

Effect of having multiple receptor shapes and charge distributions in the system: (a-b) Schematic electrostatic binding profiles of a hypothetical hydrophobic ligand (a) and charged ligand (b) to three differently-shaped sets of receptors. Each parabola represents the electrostatic binding profile toward identically shaped receptors varying in charge; there are three different shapes of receptors, leading to the three different parabolas. Note that the hydrophobic ligand has far more receptors in the space within b kcal/mol from the best binder — all three receptor shapes contribute to its promiscuity, and it is more promiscuous. Only two receptor shapes (represented by the solid and dotted parabolas) contribute to the promiscuity of the charged ligand, and it is therefore less promiscuous. (c) Plot of promiscuity vs. ligand desolvation penalty for ligands varying linearly in their charge distribution and binding rigidly to receptors varying both in their shape and charge distribution (in an unbounded charge space). Only the electrostatic component of binding was calculated in this plot. (d) Promiscuities of the 625 model ligands toward the ensemble of differently-shaped and -charged receptors are plotted against ligand desolvation penalty. Here, the full energy function was used.