Scratching the Surface: Resurfacing Proteins to Endow New Properties and Function.

Protein engineering is an emerging discipline that dovetails modern molecular biology techniques with high-throughput screening, laboratory evolution technologies, and computational approaches to modify sequence, structure, and, in some cases, function and properties of proteins. The ultimate goal is to develop new proteins with improved or designer functions for use in biotechnology, medicine, and basic research. One way to engineer proteins is to change their solvent-exposed regions through focused or random "protein resurfacing." In this review we explain what protein resurfacing is, and discuss recent examples of how this strategy is used to generate proteins with altered or broadened recognition profiles, improved stability, solubility, and expression, cell-penetrating ability, and reduced immunogenicity. Additionally we comment on how these properties can be further improved using chemical resurfacing approaches. Protein resurfacing will likely play an increasingly important role as more biologics enter clinical use, and we present some arguments to support this view.