MTD-PLS: A PLS-based variant of the MTD method. 2. Mapping ligand-receptor interactions. Enzymatic acetic acid esters hydrolysis

J Chem Inf Comput Sci. 2002 Jul-Aug;42(4):841-6. doi: 10.1021/ci010124a.

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(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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acetates / metabolism*
  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Animals
  • Computer Simulation*
  • Crystallography, X-Ray
  • Hydrolysis
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Models, Chemical
  • Quantitative Structure-Activity Relationship
  • Receptors, Drug / metabolism*
  • Static Electricity
  • Substrate Specificity

Substances

  • Acetates
  • Ligands
  • Receptors, Drug
  • Acetylcholinesterase