Three-dimensional pattern recognition: An approach to automated interpretation of electron density maps of proteins

Abstract

A procedure is outlined for reducing the high resolution electron density map of a protein to a set of connected thin lines which follow the density. The side chain representations are removed from this skeleton leaving primarily main chain, disulfide bridges and very strong hydrogen bonds. Crystallographic and local operators are used to separate one protein molecule from the neighboring chains in the crystal. Provisional α-carbon positions along the skeletal main chain are derived by application of the “4 Å rule”. The application of these methods to the 2.0 Å electron density map of ribonuclease S (Wyckoff et al., 1970) is described. The skeleton of the isolated molecule that is produced in this fashion provides a good over-all view of the three-dimensional folding of the protein. The results suggest that the skeleton representation can be a valuable supplement to the present methods of map interpretation and a significant step towards complete automation of the interpretation process. The three-dimensional pattern recognition procedures described may have much broader applications than the protein structure problem for which they have been developed.