IIT Kanpur Joins Nobel Laureate David Baker's Lab to AI-Design Miniproteins Against GPCRs

Researchers at the Indian Institute of Technology (IIT) Kanpur worked with the laboratory of Nobel Prize-winning biochemist David Baker at the University of Washington to design a new kind of small protein, called a miniprotein, that can block a group of cell-surface receptors known as G protein-coupled receptors (GPCRs). GPCRs sit on the surface of our cells and are involved in how many modern medicines work. The study, titled "De novo design of miniproteins targeting GPCRs," was published in the journal Nature.

The work demonstrates that artificial intelligence can be used to efficiently design and identify miniproteins that attach to specific GPCRs and change how the receptors behave. The team created miniproteins for several GPCRs, including two called CXCR4 and CCR5, both of which are being studied as possible drug targets for cancer and for viral infections such as HIV.

IIT Kanpur's role was to visualize how one of the designed miniproteins attaches to the CXCR4 receptor. Using cryo-electron microscopy (cryo-EM), a powerful imaging technique, at its cryo-EM facility, the researchers could see exactly how the two molecules fit together and how the miniprotein changes the receptor's behavior.

The findings show that AI-based protein design is a practical tool for drug discovery. The miniproteins made in the study are not medicines yet, and years of further testing lie ahead before any of them could reach the clinic. Even so, the study offers a workable method for designing targeted, protein-based treatments for receptors that have so far been difficult to target with drugs.