AUTOMATION OF MACROMOLECULAR MAP INTERPRETATION AND MODEL BUILDING

Tom Oldfield

University of York Molecular Simulation Inc. Heslington York YO1 5DD UK
Email : tom@yorvic.york.ac.uk, WWW personal : www.yorvic.york.ac.uk/~tom, WWW institute : www.yorvic.york.ac.uk (also www.msi.com)

Keywords: Map interpretation, model building, automated, real space torsion angle refinement, validation

Recent developments in recombinant DNA techniques, crystallisation protocols, X-ray data collection techniques and devices, and computing have led to a substantial increase in the speed and number of protein structure determinations in modern crystallographic laboratories. However, there still remains a number of key stages in the crystallographic process which limit the rate of structure determination. One of these is fitting electron density maps, either in the initial stages of tracing a chain to a new map, or in the manual rebuilding during refinement. This is a particularly onerous task, requiring many days and often weeks of working at a graphics terminal with maps and model.

The electron density applications available within the new version of QUANTA ( QUANTA 98 ), represent novel and effective tools for speeding up this process. The various modules ( X-AUTOFIT, X-LIGAND, X-SOLVATE, X-BUILD and X-POWERFIT) have been developed in close collaboration with the large number of crystallographers working on projects in the Protein Group at York. These tools provide the crystallographer with map skeletonisation, map masks, CA-tracing, fuzzy logic sequence assignment, real space torsion angle refinement using grid/gradient/Monte Carlo protcols, interactive regularisation, validation, ligand conformational searching and water fitting all in a single application.

This presentation will show :

1. how X-POWERFIT can be used for the interpretation of maps calculated with experimental phase information in a near automated fashion.
2. how model building and validation methods are merged into a single application for near automated model building.

Examples of the use of the application using real data will show that a 10-100 fold reduction in time for the initial map interpretation is common, while model building times are 10 quicker.

A summary of the other applications in QUANTA 98 for crystallographic structure determination will indicate the new ideas that speed up the overall structure determination process.

Who check the Checkers ? Four Validation Tools Applied to Eight Atomic Resolution Structures. J.Mol.Biol (1998) 276, 417-436.