Inducedjit configurational transitions in proteins can take many forms. In cases, wejind small "closures" of a loop onto the substrate In other cases, the structural changes triggered by a ligand involve large rearrangements that afect entire domains. The nature of these transitions is normally assessed by a visual analysis or in terms of simple local geometrical parameters, such as interresidue distances, backbone dihedral angles, and relative displacements between domains. This approach is limited and rather undiscriminating. In this work, we apply recently introduced ideas from macromolecular shape analysis io characterize the global shape changes accompanying "open t) c1osed"transitions in proteins. Here, we monitor two distinct properties simultaneously: molecular size and self-entanglements. The method is applied to some proteins exhibiting pairs of structurally diferent conformations (adenylate kinase, hexokinase, citrate synthuse, alcohol dehydrogenase, triosephosphate isomerase, thioredoxin, and aspartate amino-transferuse) . The conformational change associated with these proteins is classified according to an order parameter that considers various molecular shape features. The results allow one to recognize, in a nonvisual fashion, the likely occurrence of /ocal orglobal structural rearrangements. In addition, the technique provides an insight into folding features that may remain invariant during the configurational transitions. 0 I996 John Wiley & Sons, Inc.