A survey of 40 multisubunit proteins and 2 protein-protein complexes was performed to assay quantitatively the distribution of hydropathy among the exterior surface, interior, contact surface, and noncontact exterior surface of the isolated subunits. We suggest a useful way to present this distribution by using a "hydropathy level diagram." Additionally, we have devised a function called "hydropathy complementarity" to quantitate the degree to which interacting surfaces have matching hydropathy distributions. Our survey revealed the following patterns: (1) The difference in hydropathy between the interior and exterior of subunits is a fairly invariant quantity. (2) On average, the hydropathy of the contact surface is higher than that of the exterior surface, but is not greater than that of the protein as a whole. There was variation, however, among the proteins. In some instances, the contact surface was more hydrophilic than the noncontact exterior, and in a few cases the contact surface was as hydrophobic as the protein interior. (3) The average interface manifests significant hydropathy complementarity, signifying that proteins interact by placing hydrophobic centers of one surface against hydrophobic centers of the other surface, and by similarly matching hydrophilic centers. As a measure of recognition and specificity, hydropathy complementarity could be a useful tool for predicting correct docking of interacting proteins. We suggest that high hydropathy complementarity is associated with static inflexible interactions. (4) We have found that some subunits that bind predominantly through hydrophilic forces, such as hydrogen bonds, ionic pairs, and water and metal bridges, are involved in dynamic quaternary organization and allostery.

A randomized, open-label prospective study was conducted with recipients of primary cadaveric liver allografts to characterize the disposition and immunodynamics of basiliximab, an interleukin-2 receptor, alpha-chain chimeric monoclonal antibody for immunoprophylaxis of acute rejection. Patients received a total intravenous dose of 40 mg basiliximab in addition to baseline dual immunosuppression consisting of cyclosporine (INN, ciclosporin) and steroids. The central distribution volume was 5.6 +/- 1.7 L with a steady-state volume of 7.5 +/- 2.5 L. It was cleared slowly with a total body clearance of 75 +/- 24 ml/hr and an elimination half-life of 4.1 +/- 2.1 days. Basiliximab was measurable in drained ascites fluid, and clearance by this route was an average of 20% of total clearance. Total body clearance correlated positively with volume of postoperative blood loss (r = 0.5253, p = 0.0101), suggesting that bleeding may represent an additional route of drug removal. A threshold relation was observed between serum concentration of basiliximab and CD25 expression on T lymphocytes whereby complete saturation of interleukin-2 receptor alpha-chain was maintained as long as serum concentrations exceeded 0.1 microgram/ml. The duration of receptor saturation was 23 +/- 7 days after transplantation (range, 13 to 41 days).

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