[Use of frequency analysis for localization of functionally important regions of thermolysin]

A theoretical investigation of the functional topography of thermolysin molecule was carried out using frequency analysis of its primary and tertiary structures. The statistical validity of predictions was estimated for the enzyme active site, substrate-binding pocket, interdomain interface, and calcium-binding sites. It was shown that frequency analysis of primary structure could be employed to predict the localization of contiguous parts of the interdomain interface. Primary structure analysis cannot be used to search for the conformation-dependent enzyme active site and substrate-binding pocket. On the contrary, frequency analysis of interresidues contacts is not so effective for prediction of the interdomain interface as compared with active site, substrate-binding pocket, and calcium-binding sites. The set of original algorithms proposed could be used in searching for functional sites in various proteins.