A Gradient of Sitewise Diversity Promotes Evolutionary Fitness for Binder Discovery in a Three-Helix Bundle Protein Scaffold.

ABSTRACT: Engineered proteins provide clinically and industrially impactful molecules and utility within fundamental research, yet inefficiencies in discovering lead variants with new desired functionality, while maintaining stability, hinder progress. Improved function, which can result from a few strategic mutations, is fundamentally separate from discovering novel function, which often requires large leaps in sequence space. While a highly diverse combinatorial library covering immense sequence space would empower protein discovery, the ability to sample only a minor subset of sequence space and the typical destabilization of random mutations preclude this strategy. A balance must be reached. At library scale, compounding several destabilizing mutations renders many variants unable to properly fo

SUBMITTER: Woldring DR 

PROVIDER: S-EPMC5521020 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature