Acta Crystallographica Section D

Biological Crystallography

Volume 61, Part 10 (October 2005)

research papers

Acta Cryst. (2005). D61, 1354-1363 [ doi:10.1107/S0907444905023152 ]

Automated crystallographic ligand building using the medial axis transform of an electron-density isosurface

J. Aishima, D. S. Russel, L. J. Guibas, P. D. Adams and A. T. Brunger

Abstract: Automatic fitting methods that build molecules into electron-density maps usually fail below 3.5 Å resolution. As a first step towards addressing this problem, an algorithm has been developed using an approximation of the medial axis to simplify an electron-density isosurface. This approximation captures the central axis of the isosurface with a graph which is then matched against a graph of the molecular model. One of the first applications of the medial axis to X-ray crystallography is presented here. When applied to ligand fitting, the method performs at least as well as methods based on selecting peaks in electron-density maps. Generalization of the method to recognition of common features across multiple contour levels could lead to powerful automatic fitting methods that perform well even at low resolution.

Keywords: protein-ligand complexes; graph matching; conformational search; medial axis transform.