This project has focused on the analysis of amino acid and nucleic acid sequence data as it pertains to molecular biology and molecular evolution. Continuing areas of interest include: i) The development of computational tools for molecular biologists. We have continued to refine earlier sequence comparison algorithms with significant improvements in sensitivity. We are also developing a method for the simultaneous alignment of up to five amino acid sequences. ii) We have analysed the variation in the solvent accessibility and hydrophobicity of the amino acids along the sequences of 58 soluble globular proteins with known tertiary structure. We find a significant tendency for clustering of accessibilities along the sequence but that hydrophobicities are distributed randomly. These results suggest severe limitations on the power of sequence analysis tools which use average hydrophobicity scores to predict solvent accessibilities. iii) We are studying the patterns of sequence conservation in protein families to develop improved methods of detecting evolutionary relationships, structural similarities, as well as the minimal differences necessary for specific functional differences.
