Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling

J Comput Aided Mol Des. 2001 Dec;15(12):1065-83. doi: 10.1023/a:1015941316283.

Abstract

A method is described for the rapid and automatic analysis of flexible molecular alignments using multidimensional scaling and a normalized scoring scheme. A projection scheme was devised to separate orientational and conformational effects. It is shown that the approach can be utilized for the identification of common binding orientations or to the study of differences in partioning behavior. It is suggested that the method can be employed as a novel approach exploring molecular similarity as a dynamic property, so that it includes aspects of motion (by way of mutual orientations), conformations and molecular properties.

MeSH terms

  • Antiviral Agents / chemistry
  • Binding Sites
  • Carbonic Anhydrases / metabolism
  • Computer Simulation
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • GABA Antagonists / chemistry
  • Isomerism
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Morphine Derivatives / chemistry
  • Permeability
  • Thermolysin / antagonists & inhibitors

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • GABA Antagonists
  • Ligands
  • Morphine Derivatives
  • morphine-6-glucuronide
  • Thermolysin
  • Carbonic Anhydrases
  • morphine-3-glucuronide