MTD-PLS: A PLS-Based Variant of the MTD Method, 2. Mapping Ligand-Receptor Interactions. Enzymatic Acetic Acid Esters Hydrolysis

The PLS variant of the MTD method (T. I. Oprea et al., SAR QSAR Environ. Res. 2001, 12, 75-92) was applied to a series of 25 acetylcholinesterase hydrolysis substrates. Statistically significant MTD-PLS models (q(2) between 0.7 and 0.8) are in agreement with previous MTD models, with the advantage that local contributions are understood beyond the occupancy/nonoccupancy interpretation in MTD. A "chemically intuitive" approach further forces MTD-PLS coefficients to assume only negative (or zero) values for fragmental volume descriptors and positive (or zero) values for fragmental hydrophobicity descriptors. This further separates the various kinds of local interactions at each vertex of the MTD hypermolecule, making this method suitable for medicinal chemistry synthesis planning.