title: Comparison of protein-protein interactions in serine protease-inhibitor and antibody-antigen complexes: implications for the protein docking problem.
abstract: The protein-protein interaction energy of 12 nonhomologous serine protease-inhibitor and 15 antibody-antigen complexes is calculated using a molecular mechanics formalism and dissected in terms of the main-chain vs. side-chain contribution, nonrotameric side-chain contributions, and amino acid residue type involvement in the interface interaction. There are major differences in the interactions of the two types of protein-protein complex. Protease-inhibitor complexes interact predominantly through a main-chain-main-chain mechanism while antibody-antigen complexes interact predominantly through a side-chain-side-chain or a side-chain-main-chain mechanism. However, there is no simple correlation between the main-chain-main-chain interaction energy and the percentage of main-chain surface area buried on binding. The interaction energy is equally effected by the presence of nonrotameric side-chain conformations, which constitute approximately 20% of the interaction energy. The ability to reproduce the interface interaction energy of the crystal structure if original side-chain conformations are removed from the calculation is much greater in the protease-inhibitor complexes than the antibody-antigen complexes. The success of a rotameric model for protein-protein docking appears dependent on the extent of the main-chain-main-chain contribution to binding. Analysis of (1) residue type and (2) residue pair interactions at the interface show that antibody-antigen interactions are very restricted with over 70% of the antibody energy attributable to just six residue types (Tyr > Asp > Asn > Ser > Glu > Trp) in agreement with previous studies on residue propensity. However, it is found here that 50% of the antigen energy is attributable to just four residue types (Arg = Lys > Asn > Asp). On average just 12 residue pair interactions (6%) contribute over 40% of the favorable interaction energy in the antibody-antigen complexes, with charge-charge and charge/polar-tyrosine interactions being prominent. In contrast protease inhibitors use a diverse set of residue types and residue pair interactions.
authors: Department of Biochemistry and Molecular Biology, University College London, United Kingdom. jackson@biochem.ucl.ac.uk
authors: R M
authors: RM
authors: Jackson
mesh_terms: D000936:Antigen-Antibody Complex / Q000737:chemistry*; D015394:Molecular Structure; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000936:Antigen-Antibody Complex; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases