THE INFORMATION-CONTENT OF 2D AND 3D STRUCTURAL DESCRIPTORS RELEVANT TO LIGAND-RECEPTOR BINDING

We have previously studied the ability of various structural descripto rs to distinguish between biologically active and inactive compounds ( ref 1). This paper examines the degree to which these descriptors enco de information relevant to the forces of ligand-receptor binding, name ly hydrophobic, dispersion, electrostatic, steric, and hydrogen bondin g interactions. This is assessed by the ability to accurately predict values for physical properties of a structure related to each of the i nteractions, from the known values for other structures which are show n to be structurally similar to the first by the descriptor in questio n. Our results suggest that the differences we observed in the ability of descriptors to separate active from inactive molecules may be expl ained by the degree to which they encode information relevant to ligan d-receptor binding. In particular we found that the MACCS structural k ey descriptor implicitly contains a great deal of information relevant to each type of interaction.