Emergence of specific binding and catalysis from a designed generalist binding protein.

ABSTRACT: The evolution of binding and catalysis played a central role in the emergence of life. While natural proteins have finely tuned affinities for their primary ligands, they also bind weakly and promiscuously to other molecules, which serve as starting points for stepwise, incremental evolution of entirely new specificities. Thus, modern proteins emerged from the joint exploration of sequence and structural space. The ability of natural proteins to bind small molecule fragments in well-defined geometries has been widely evaluated using methods including crystallographic fragment screening. However, this approach had not been applied to de novo proteins. Here, we apply this method to explore the binding specificity of a de novo small molecule-binding protein ABLE. As in Nature, w

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11838529 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature