We propose an algorithm for determining the domain structure of globular proteins. The method obviates the use of complicated geometrical criteria with numerous fitting parameters, as it relies on the entirely physical model van der Waals interactions, which can be represented analytically with the distribution of electron density. Various levels of hierarchy in the protein spatial structure are discerned by analysis of the energy interaction between structural units of different scales. The algorithm readily and accurately locates domains formed by continuous segments of the protein chain as well as those comprising nonsequential segments, and sets no limit to the number of segments included in a domain. We have analyzed 309 protein structures. The domains delineated with our approach may coincide with reference definition at different levels of the globule hierarchy. Along with defining the domain structure, our approach allows one to consider the protein spatial structure in terms of the spatial distribution of the interaction energy in order to establish the correspondence between the hierarchy of energy distribution and the hierarchy of structural elements.

This work was supported by Russian Foundation for Basic Research grant N 97-04-49707.