Theoretical study of hinge bending in L-arabinose-binding protein. Internal energy and free energy changes.

The L-arabinose-binding protein of Escherichia coli is a periplasmic component of the L-arabinose transport system. Its three-dimensional structure has been determined by x-ray diffraction and shown to have two globular domains and a connecting hinge. These structural features enclose a cleft in which the L-arabinose-binding site is located. The flexibility of the protein hinge that allows hinge-bending motion is investigated here by theoretical analysis of the changes in conformational energy and molecular structure that accompany the opening and closing of the cleft. The hinge of the molecule is found to be quite permissive in that only moderate increases in the internal energy occur upon opening the cleft. Solvation changes of charged groups on the cleft-facing surfaces of the lobes are estimated to make important contributions to the overall energetics of the system. The results indicate that an open conformation for the unliganded protein is stabilized by the exposure and solvation of charged groups in the cleft, and that the cleft is induced to close upon ligand binding. This picture is consistent with experimental data on the structure and the binding kinetics of L-arabinose-binding protein, and provides a physical framework for interpreting such data.