RESEARCH ARTICLES Protein Domain Movements: Detection of Rigid Domains and Visualization of Hinges in Comparisons of Atomic Coordinates

ABSTRACT The activity of many proteins induces conformational transitions by hinge-bending, which involves the movement of rela-tively rigid parts of a protein about flexible joints. We present an algorithm to identify and visualize the movements of rigid domains about common hinges in proteins. In comparing two structures, the method partitions a protein into domains of preserved geometry. The do-mains are extracted by an adaptive selection procedure using least-squares fitting. The user can maintain the spatial connectivity of the domains and filter significant structural differ-ences (domain movements) from noise in the compared sets of atomic coordinates. The algo-rithm subsequently characterizes the relative movements of the found domains by effective rotation axes (hinges). The method is applied to several known instances of domain move-ments in protein structures, namely, in lactofer-rin, hexokinase, actin, the extracellular do-mains of human tissue factor, and the receptor of human growth factor. The results are visual-ized with the molecular graphics package VMD (Humphrey et al., J. Mol. Graphics 14(1):33–38, 1996). Applications of the algorithm to the analysis of conformational changes in proteins and to biomolecular docking are discussed. Proteins 29:1–14, 1997. r 1997 Wiley-Liss, Inc. Key words: protein architecture; hinge-bend-ing; lactoferrin; hexokinase; actin; human tissue factor; human growth facto