Journal of Computer-Aided Molecular Design

, Volume 14, Issue 6, pp 573–591 | Cite as

A novel method of aligning molecules by local surface shape similarity

  • D.A. Cosgrove
  • D.M. Bayada
  • A.P. Johnson


A novel shape-based method has been developed for overlaying a series of molecule surfaces into a common reference frame. The surfaces are represented by a set of circular patches of approximately constant curvature. Two molecules are overlaid using a clique-detection algorithm to find a set of patches in the two surfaces that correspond, and overlaying the molecules so that the similar patches on the two surfaces are coincident. The method is thus able to detect areas of local, rather than global, similarity. A consensus overlay for a group of molecules is performed by examining the scores of all pairwise overlays and performing a set of overlays with the highest scores. The utility of the method has been examined by comparing the overlaid and experimental configurations of 4 sets of molecules for which there are X-ray crystal structures of the molecules bound to a protein active site. Results for the overlays are generally encouraging. Of particular note is the correct prediction of the `reverse orientation' for ligands binding to human rhinovirus coat protein HRV14.


Reference Frame Coat Protein Local Surface Shape Similarity Constant Curvature 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • D.A. Cosgrove
    • 1
  • D.M. Bayada
    • 2
  • A.P. Johnson
    • 2
  1. 1.AstraZenecaCheshireU.K.
  2. 2.School of ChemistryUniversity of LeedsLeedsU.K.

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