Computational Design of Ligand Binding Proteins

Brian Kuhlman, Tim Jacobs, Tom Linskey

Barry L. Stoddard

Naturally occurring proteins often consist of multiple distinct domains joined by linker regions. Similarly, the ability to combine globular protein domains through engineered linkers would allow the creation of a wide variety of complex and useful multifunctional proteins. Recent advances in computational design of protein structures have enabled highly accurate design of novel protein structures. In this chapter we outline a computational protocol for the de novo design of protein linkers, and apply this protocol to the design of a helical linker between two rigid protein domains.