ABSTRACT
Electrostatic forces are involved in a wide variety of molecular interactions that are of biological interest, including, among others, DNA-Protein interactions, protein folding, and the interactions between enzymes and their substrates and inhibitors. In this work, the interaction between papain and an inhibitor, leupeptin, is analyzed from the point of view of their electrostatic interaction. The computations enable one to suggest that negatively charged amino acids located in the region of the active site are responsible for creating an environment that enables efficient binding of the inhibitor. This binding occurs despite the fact that the net global charge of both molecules is positive; an explanation for this apparent contradiction is proposed.
Subject(s)
Computer Simulation , Cysteine Proteinase Inhibitors/chemistry , Leupeptins/chemistry , Models, Molecular , Papain/chemistry , Binding Sites/physiology , Macromolecular Substances , Models, Chemical , Papain/antagonists & inhibitors , Protein Binding/physiology , Static ElectricityABSTRACT
The electrostatic interaction of the Phospholipase A2 (PLA2)-membrane complex in the presence and absence of calcium is analysed by the computation of the electrostatic profiles of the components and the complex. The electrostatic potential was computed by using of the program MOLPOT that implement the boundary element method to solve the electrostatic problem. It considers a closed surface in three dimensions that contains the macromolecule that follows as close as possible the macromolecule shape. The results show that the presence of calcium ions contributes to the stability of the complex and at the same time creates a favourable electrostatic potential pattern that may be favourable for the lipolysis of the membrane components.
