Stability and CDR composition biases enrich binder functionality landscapes.

ABSTRACT: The rugged protein sequence-function landscape complicates efforts, both in nature and in the laboratory, to evolve protein function. Protein library diversification must strike a balance between sufficient variegation to thoroughly sample alternative functionality versus the probability of mutant destabilization below an expressible threshold. In this work, we explore the sequence-function landscape in the context of screening for molecular recognition from an Ig scaffold library. The fibronectin type III domain is used to explore the impact of two sequence diversification strategies: (a) partial wild-type conservation at structurally important positions within the paratope region and (b) tailored amino acid composition mimicking antibody binding-site composition at putative paratope posi

SUBMITTER: Hackel BJ 

PROVIDER: S-EPMC3927142 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature