Electrostatics in Protein Engineering and Design

The electrostatic interactions between charged atoms in natural proteins play a central role in specifying protein topology, modulating stability of the molecule, and allowing for the impressive catalytic properties of enzymes. In this chapter, we discuss how protein engineers use the principles of electrostatics and computational protein modeling to develop new proteins for biomedical and biotechnological applications. First, a general introduction is given to familiarize the reader with the important factors to consider in protein electrostatics, and the nature of these electrostatic forces. The next section describes various levels of theory used for modeling electrostatics in proteins. The last sections focus on specific applications in two conceptual classes: the engineering of ionic interactions (1) on protein surfaces, and (2) within the hydrophobic protein core. In both cases, the aim is to promote stability or to control molecular recognition.