De novo design of BMP mimics.

Abstract

In traditional structure-guided drug designs, scientists often design drugs to target the active site of proteins of interest with detailed knowledge about the active site. However, despite the success rate, targeting the active site often leads to off-target side effects. With the development of protein binder design in the Baker Lab, one may imagine rewiring this drug development process by using de novo designed binders to regulate cell signaling pathways. Here I will present my efforts toward designing agonists/antagonists targeting different cell signaling pathways. I will focus on our efforts in developing bone morphogenetic protein 2/9/10 (BMP2/9/10) mimics, which are a group of growth factors to constitute a group of morphogenetic and angiogenetic signals. Recombinant human BMPs are used in orthopedics including oral surgery and spinal surgery. This project aims to specifically activate/inhibit BMP signaling pathways of interest by designing protein binders targeting specific BMP receptors, therefore, providing new therapeutics.