Structure Prediction and Visualization in Molecular Biology
Candidate: Christopher Poultney
Advisor: Dennis Shasha

Abstract

The tools of computer science can be a tremendous help to the working biologist. Two broad areas where this is particularly true are visualization and prediction. In visualization, the size of the data involved often makes meaningful exploration of the data and discovery of salient features difficult and time-consuming. Similarly, intelligent prediction algorithms can greatly reduce the lab time required to achieve significant results, or can reduce an intractable space of potential experiments to a tractable size.

Whereas the thesis discusses both a visualization technique and a machine learning problem, the thesis presentation will focus exclusively on the machine learning problem: prediction of temperature-sensitive mutations from protein structure. Temperature-sensitive mutations are a tremendously valuable research tool particularly for studying genes such as yeast essentially genes. To date, most methods for generating temperature-sensitive mutations involve large-scale random mutations followed by an intensive screening and characterization process. While there have been successful efforts to improve this process by rational design of temperature-sensitive proteins, surprisingly little work has been done in the area of predicting those mutations that will exhibit a temperature-sensitive phenotype. We describe a system that, given the structure of a protein of interest, uses a combination of protein structure prediction and machine learning to provide a ranked "top 5" list of likely candidates for temperature-sensitive mutations.