The framework of computational protein design

Abstract

Computational protein design (CPD) has established itself as a leading field in basic and applied science with a strong coupling between the two. Proteins are computationally designed from the level of amino acids to the level of a functional protein complex. Design targets range from increased thermo- (or other) stability to specific requested reactions such as protein–protein binding, enzymatic reactions, or nanotechnology applications. The design scheme may encompass small regions of the proteins or the entire protein. In either case, the design may aim at the side-chains or at the full backbone conformation. Herein, the main framework for the process is outlined highlighting key elements in the CPD iterative cycle. These include the very definition of CPD, the diverse goals of CPD, components of the CPD protocol, methods for searching sequence and structure space, scoring functions, and augmenting the CPD with other optimization tools. Taken together, this chapter aims to introduce the framework of CPD.