Electrostatic recognition between enzyme and inhibitor: Interaction between papain and leupeptin

Electrostatic forces are involved in a wide variety of molecular interactio ns that are of biological interest, including, among others, DNA-Protein in teractions, protein folding, and the interactions between enzymes and their substrates and inhibitors. In this work, the interaction between papain an d an inhibitor, leupeptin, is analyzed from the point of view of their elec trostatic interaction. The computations enable one to suggest that negative ly charged amino acids located in the region of the active site are respons ible for creating an environment that enables efficient binding of the inhi bitor. This binding occurs despite the fact that the net global charge of b oth molecules is positive; an explanation for this apparent contradiction i s proposed. (C) 2001 Academic Press.