Browse Theses

I have designed and implemented a tool for biochemists to use for interpreting electron density maps of crystallized proteins. My work has been concentrated on the representation for electron density maps and on the man-machine interface.

Interpreting an electron density map is a difficult pattern recognition problem requiring specialized knowledge of protein structure and global views of the map. The tool is an interactive graphics system in which the human makes strategy decisions and does global pattern recognition, naming and pointing to recognized features in the map. These features belong to a hierarchy of objects natural to the problem. The computer does local, anchored pattern recognition for indicated features, displays the map in a ridge line representation using color to encode the map's interpretation, and automatically builds a molecular model as the user identifies residues.

A ridge line representation for maps was chosen because of the close correspondence of ridge lines to stick-figure models of molecules, because of the relatively few line segments required to display them, and because of the ease with which the density threshold can be changed in real time.

Three different sets of people have interpreted electron density maps using this tool. A computer scientist (myself) interpreted a 2.5 A map of Staphyloccal nuclease in 26 hours. This was the first map I had ever interpreted. A highly-skilled professional biochemist interpreted a 3.0 A map of cytochrome b5 in 9 hours. A group of three biochemistry graduate students and post-doctoral fellows interpreted a 2.8 A map of cytochrome c550 in 22 hours. These three successful interpretations done in such relatively short times have shown that the system design is a good and useful one for this application.

The contributions of this work to computer science are (1) a documented example of a good man-machine interface, (2) a detailed discussion of the major design decisions that I made, and (3) a demonstration of the usefulness of a ridge line representation for a scalar function of three variables.