Protein library design and screening: working out the probabilities.

In designing protein libraries for selection, we must coordinate our capacity to create a large diversity of protein variants with the physical limitations of what we can actually screen. This chapter aims to bring the language of probabilities into the protein engineer's laboratory to answer some of our common questions: How can we most efficiently design a library? What fraction of the theoretical library diversity have we actually sampled at the end of the day? What is the probability of missing an individual of the library? Are the mutations present in the variants we have selected statistically meaningful or the product of random variation? The computation of these criteria throughout the process of experimental protein engineering will enable us to better design and evaluate the products of our libraries of protein variants.