MOLECULAR SCENE ANALYSIS - APPLICATION OF A TOPOLOGICAL APPROACH TO THE AUTOMATED INTERPRETATION OF PROTEIN ELECTRON-DENSITY MAPS

Methods to assist in the spatial and visual analysis of electron-densi ty maps have been investigated as part of a project in molecular scene analysis [Fortier, Castleden, Glasgow, Conklin, Walmsley, Leherte & A llen (1993). Acta Cryst. D49, 168-178]. In particular, the usefulness of the topological approach for the segmentation of medium-resolution (3 angstrom) maps of proteins and their interpretation in terms of str uctural motifs has been assessed. The approach followed is that propos ed by Johnson [Johnson (1977). ORCRIT. The Oak Ridge Critical Point Ne twork Program. Chemistry Division, Oak Ridge National Laboratory, USA] which provides a global representation of die electron-density distri bution through the location, identification and linkage of its critica l points. In the first part of the study, the topological approach was applied to calculated maps of three proteins of small to medium size so as to develop a methodology that could then be used for analyzing m aps of medium resolution. The methodology was then applied to both cal culated and experimental maps of penicillopepsin at 3 angstrom resolut ion. The study shows that the networks of critical points can provide a useful segmentation of the maps, tracing the protein main chains and capturing their conformation. In addition, these networks can be pars ed in terms of secondary-structure motifs, through a geometrical analy sis of the critical points. The procedure adopted for secondary-struct ure recognition, which was phrased in terms of geometry-based rules, p rovides a basis for a further automated implementation of a more compl ete set of recognition operations through the use of artificial-intell igence techniques.