Hierarchy of the interaction energy distribution in the spatial structure of globular proteins and the problem of domain definition

An algorithm for determining of protein domain structure is proposed. Domai n structures resulted from the algorithm application have been obtained and compared with available data. The method is based on entirely physical mod el of van der Waals interactions that reflects as illustrated in this work the distribution of electron density. Various levels of hierarchy in the pr otein spatial structure are discerned by analysis of the energy interaction between structural units of different scales. Thus the level of energy hie rarchy plays role of sole parameter, and the method obviates the use of com plicated geometrical criteria with numerous fitting parameters. The algorit hm readily and accurately locates domains formed by continuous segments of the protein chain as well as those comprising non-sequential segments, sets no limit to the number of segments in a domain. We have analyzed 309 prote in structures. Among 277 structures for which our results could be compared with the domain definitions made in other works, 243 showed complete or pa rtial coincidence, and only in 34 cases the domain structures proved substa ntially different. The domains delineated with our approach may coincide wi th reference definition at different levels of the globule hierarchy. Along with defining the domain structure, our approach allows one to consider th e protein spatial structure in terms of the spatial distribution of the int eraction energy in order to establish the correspondence between the hierar chy of energy distribution and the hierarchy of structural elements.