7] Surface and electrostatics of cutinases

Abstract

The surface of a protein constitutes the interface through which the protein senses the environment surrounding it. Therefore, it should be central to any study aiming at a better understanding of the molecular basis for the interaction between an enzyme and its substrate or inhibitor, a receptor and its ligand, or any other type of molecular recognition. In the study of biological macromolecular systems it is becoming increasingly evident that electrostatic interactions contribute significantly to folding, conformational stability, enzyme activity, and binding energies as well as to protein-protein interactions. This chapter presents approaches to modeling electrostatic interactions in biomolecular systems. It describes an approach for the calculation of the pk a values of titratable groups in proteins. The chapter also presents some methods that can be used to map and study the amino acid distribution on the molecular surface of proteins. The combination of graphic visualization of the electrostatic fields with the knowledge about the location of key residues on the protein surface allows envisioning atomic models for enzyme function. Some of these methods are applied to the enzymes of the cutinase family.