A rapid test for identification of autonomous folding units in proteins

The structure of a protein is dictated by a large number of weak interactio ns that cooperatively stabilize the native state. Usually, excised fragment s smaller than a domain have Little if any residual structure. When autonom ous units of structure are found within domains, this challenges common ass umptions about the cooperativity of protein structure. Such autonomous fold ing units (AFUs) are of wide interest and have applications in protein engi neering and as simple model systems for studying the determinants of stabil ity and specificity. A new method of identifying AFUs within proteins is pr esented here. The rapid autonomous fragment test (RAFT) identifies AFUs bas ed on analysis of inter-residue contacts present in the three-dimensional s tructure of a protein. RAFT is fast enough to mine the entire PDB for AFUs and provide a library of potential small stable folds. We show that RAFT is able to predict whether a protein fragment will be structured if isolated from its parent domain. (C) 2000 Academic Press.