Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates.

The activity of many proteins induces conformational transitions by hinge-bending, which involves the movement of relatively 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 domains 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 differences (domain movements) from noise in the compared sets of atomic coordinates. The algorithm subsequently characterizes the relative movements of the found domains by effective rotation axes (hinges). The method is applied to several known instances of domain movements in protein structures, namely, in lactoferrin, hexokinase, actin, the extracellular domains of human tissue factor, and the receptor of human growth factor. The results are visualized 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.