Background: The mechanisms that allow or constrain protein movement have not been understood. Here we study interdomain interactions in proteins to investigate hinge-bending motions.
Results: We find a limited number of salt bridges and hydrogen bonds at the interdomain interface, in both the "closed" and the "open" conformations. Consistently, analysis of 222 salt bridges in an independently selected database indicates that most salt bridges form within rather than between independently folding hydrophobic units. Calculations show that these interdomain salt bridges either destabilize or only marginally stabilize the closed conformation in most proteins. In contrast, the nonpolar buried surface area between the moving parts can be extensive in the closed conformations. However, when the nonpolar buried surface area is large, we find that at the interdomain interface in the open conformation it may be as large or larger than in the closed conformation. Hence, the energetic penalty of opening the closed conformation is overcome. Consistently, a large nonpolar surface area buried in the closed interdomain interface accompanies limited opening of the domains, yielding a larger interface.
Conclusions: Short-range electrostatic interactions are largely absent between moving domains. Interdomain nonpolar buried surface area may be large in the closed conformation, but it is largely offset by the area buried in the open conformation. In such cases the opening of the domains appears to be relatively small. This may allow prediction of the extent of domain opening. Such predictions may have implications for the shape and size of the binding pockets in drug/protein design.