A recipe for ligand-binding proteins

Abstract

Cellular cross-talk, enzymatic catalysis and regulation of gene expression all depend on molecular recognition. A method that allows the design of proteins with desired recognition sites could thus be revolutionary. See Letter p.212 Current approaches to the design of ligand-binding proteins for medical or biotechnological applications involve raising antibodies against a target antigen in immunized animals and/or performing directed evolution experiments on proteins with pre-existing, low affinity for the desired ligand. This paper describes a general method for the computational design of small molecule binding proteins that the authors use to design high-affinity and highly selective binding sites for the steroid digoxigenin, a cardiac glycoside used to treat heart disease. Using this method it should be possible to rapidly create small molecule receptors for synthetic biology applications, therapeutic scavengers for toxic compounds in vivo and robust ligand-binding domains for diagnostic devices.