Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model.
A method of calculating the electrostatic potential energy between two molecules, using finite difference potential, is presented. A reduced charge set is used so that the interaction energy can be calculated as the two static molecules explore their full six-dimensional configurational space. The energies are contoured over surfaces fixed to each molecule with an interactive computer graphics program. For two crystal structures (trypsin-trypsin inhibitor and anti-lysozyme Fab-lysozyme), it is found that the complex corresponds to highly favourable interacting regions in the contour plots. These matches arise from a small number of protruding basic residues interacting with enhanced negative potential in each case. The redox pair cytochrome c peroxidase-cytochrome c exhibits an extensive favourably interacting surface within which a possible electron transfer complex may be defined by an increased electrostatic complementarity, but a decreased electrostatic energy. A possible substrate transfer configuration for the glycolytic enzyme pair glyceraldehyde phosphate dehydrogenase-phosphoglycerate kinase is presented.
Warwicker
J
J
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.
D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D003578:Cytochrome-c Peroxidase / Q000378:metabolism; D004734:Energy Metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008958:Models, Molecular; D009113:Muramidase / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000378:metabolism
D003574:Cytochrome c Group; D011506:Proteins; D014361:Trypsin Inhibitors; D003578:Cytochrome-c Peroxidase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010735:Phosphoglycerate Kinase; D009113:Muramidase; D014357:Trypsin