ANALYSIS OF DOMAIN STRUCTURAL CLASS USING AN AUTOMATED CLASS ASSIGNMENT PROTOCOL

The extent to which the contemporary dataset of protein structures can be segregated into four structural ''classes'' as originally defined by Levitt & Chothia in 1976 is examined and a simple method presented for the assignment of protein domains into these classes. Assignments are based on known three-dimensional structures, and for successful as signment it was found that helix/sheet content, contacts between secon dary structures and their sequential order had to be used. The procedu re attempts to maximise the automatic separation into classes for a da taset of 197 manually classified, non-homologous domains. It was found that approximately 90% of the structures were classified automaticall y; the remainder were borderline and were left for manual inspection. The method was then applied to a test set of 43 protein domains with s imilar results. The data support the concept of distinct classes of pr otein structure, although a few intermediate structures are found, dem onstrating that it is possible to define relatively simple parameters complying with commonly accepted nomenclature that automatically defin e 90% of protein domains with essentially 100% accuracy. However, re-e xamination of the data also suggested that the previously separate alp ha/beta and alpha + beta classes show considerable overlap and are mor e naturally represented as a single alpha beta class. This large alpha beta class can then be most easily subdivided by consideration of whe ther the sheets are mainly parallel, antiparallel or mixed. The correl ation between structural class and function is discussed, together wit h the conservation of class within a sequence superfamily. This repres ents the first step in an automated phenetic description of protein st ructure complementing the usual phylogenetic approach to protein struc ture classification. (C) 1996 Academic Press Limited