title: MTD-PLS: a PLS-based variant of the MTD method. II. Mapping ligand-receptor interactions. Enzymatic acetic acid esters hydrolysis
abstract: 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/sup 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
keyphrases: PLS-based variant enzymatic acetic acid esters hydrolysis acetylcholinesterase hydrolysis substrates MTD-PLS models fragmental volume descriptors fragmental hydrophobicity descriptors hypermolecule medicinal chemistry synthesis planning minimum topological difference method ligand-receptor interactions mapping chemically intuitive approach steric misfit additive approach intermolecular force categories regression coefficients ligand binding affinity hydrogen bonding polarizabilities statistical model stability