MTD-PLS: a PLS-based variant of the MTD method. A 3D-QSAR analysis of receptor affinities for a series of halogenated dibenzoxin and biphenyl derivatives. Academic Article uri icon

start page

  • 75

end page

  • 92

abstract

  • MTD-PLS, the Partial Least Squares (PLS) variant of the Minimum Topological Difference (MTD) method is described. In MTD-PLS, molecules are characterised not only by the occupancy or nonoccupancy of the hypermolecular vertices (as in classical MTD), but also by additional descriptors for each vertex: fragmental van der Waals volumes, fragmental hydrophobicities, partial atomic charges, etc. This method was applied to a series of 73 polyhalogenated derivatives of dibenzo-p-dioxine, dibenzofuran and biphenyl (induction of aryl hydrocarbon hydrolase and affinities to rat cytosolic receptor), previously studied by MTD. The separation of steric, hydrophobic, and electrostatic effects was achieved retranslating from the latent variable space into a linear combination of the initial structural variables. The MTD-PLS method yields more detailed results compared to classical MTD, indicating the importance of electrostatic effects at some substituent positions.

date/time value

  • 2001

Digital Object Identifier (DOI)

  • 10.1080/10629360108035372

PubMed Identifier

  • 11697061

volume

  • 12

number

  • 1-2

keywords

  • Binding Sites
  • Dioxins
  • Hydrocarbons, Halogenated
  • Least-Squares Analysis
  • Ligands
  • Maximum Tolerated Dose
  • Structure-Activity Relationship