The molecular mechanism of protein synthesis remains unknown. Because of the fundamental nature of this problem its solution would have far reaching implications in the health sciences. A major current objective of workers in the ribosome field is to determine the structure of the Escherichia coli ribosome in the greatest detail possible. This information will provide important new insights to protein/nucleic acid interactions and to a comprehension of the molecular mechanics of translation itself. The specific goal of the research proposed here is to elucidate likely base-base tertiary interactions in and among the ribosomal RNAs. It is not expected that all such tertiary interactions can be identified at this time nor is it expected that the tertiary structure of the ribosome as a whole can be deduced by the methods described here. It is expected however that we can identify candidate interactions that are highly likely to be biologically significant. These interactions would then be subject to experimental test by methods we propose here and by methods invoked by other investigators as well. The essence of the approach will be to identify candidate tertiary interactions by a comparative tactic. These will subsequently be evaluated for compatibility with other data and the geometric constraints imposed by three dimensional space. In cases where the available statistical data is insufficient, additional comparative data will be sought. The feasibility of conducting direct experimental studies to evaluate the importance of predicted tertiary interactions will be demonstrated in E. coli 5S rRNA.
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