Evaluation of ligand overlap by atomic parameters.

The overlap of ligand atoms has been analyzed for 32 common enzyme systems. The ligand alignment was determined by superposition of the experimentally determined protein structures. Comparison of the overlapping atoms in terms of atomic contribution to partition coefficient and molar refractivity shows that in most cases ligand atoms overlap with atoms of a similar nature, as should be expected. A new statistic, the mean maximal atomic deviation (MeMAD), is determined and validated for each system studied by comparison to randomized data. In almost all cases, the MeMAD is well separated from the randomized outcome. This result indicates the validity of the atom-based physicochemical parameters in 3-D QSAR methods.