Exploring and designing protein function with restricted diversity

Combinatorial libraries with restricted diversity can be used to rapidly map binding energetics across protein interfaces. Shotgun scanning strategies have been used for alanine scanning and for alternative mutagenesis schemes that provide high-resolution functional views of binding interfaces. In addition, synthetic antibodies have been derived from naïve libraries restricted to a binary code to explore the minimal requirements for molecular recognition. These studies shed light on the underlying principles governing molecular recognition, and provide rapid yet quantitative alternatives to conventional biophysical methods for exploring protein structure and function.