Influence of conformation on the representation of small flexible molecules at low resolution: alignment of endothiapepsin ligands

J Comput Aided Mol Des. 2005 Jul;19(7):525-49. doi: 10.1007/s10822-005-9005-3. Epub 2005 Nov 16.

Abstract

In this contribution, we discuss a molecular representation mode for the generation of reduced descriptions of flexible molecules in various conformations. The representations of the endothiapepsin ligands are constituted by graphs of peaks obtained through a hierarchical merging algorithm which combines the location of promolecular electron density (ED) maxima with the decomposition of the molecular structures into fragments. The representations are then aligned through the use of a Monte Carlo/Simulated Annealing procedure. The evaluation function of the alignment solutions is based on the local density values of the peaks and their inter-distances. The applications show that the alignment of a given molecule onto itself, in a different conformation, is successful when a pseudo-topological path length is considered in the evaluation function of the solution, while Cartesian distances are more adapted to the scoring for alignments of two different molecules in their co-crystallized conformation. Results are compared with the available literature data.

MeSH terms

  • Algorithms
  • Aspartic Acid Endopeptidases / chemistry*
  • Ligands
  • Models, Molecular
  • Molecular Conformation*

Substances

  • Ligands
  • Aspartic Acid Endopeptidases
  • Endothia aspartic proteinase