Researchers from the Indian Institute of Technology Kanpur (IIT Kanpur), together with the laboratory of Nobel laureate Professor David Baker at the University of Washington, have developed miniproteins capable of blocking GPCR receptors.
These receptors, located on the cell surface, play a key role in signal transduction and serve as targets for many modern drugs. Traditional search for molecules for them requires testing millions of compounds in the laboratory — a process that is long and costly.
The new approach uses artificial intelligence to design miniproteins that are highly likely to bind to specific GPCRs. Then only the most promising candidates are tested in laboratory conditions. This significantly reduces the time and cost of the early stages of drug discovery.
The study titled "De novo design of miniproteins targeting GPCRs" is published in the journal Nature. The team created miniproteins for the CXCR4 and CCR5 receptors, which are being studied as potential targets in cancer and HIV infections.
At IIT Kanpur, cryo-electron microscopy was used to visualize how one of the miniproteins attaches to CXCR4 and affects its function. This confirmed the accuracy of the computational design.
The work was led by the laboratory of Professor Baker, a Nobel Prize laureate in Chemistry in 2024. Key contributions were made by Professor Arun K. Shukla from IIT Kanpur along with the team: Dr. Ramanuj Banerjee, Manishankar Ganguly, Annu Dalal, Sudha Mishra, and Shachi Sinha. The research was supported by Anusandhan National Research Foundation, Department of Biotechnology, and Lady Tata Memorial Trust.
Although these miniproteins are not yet drugs and years of trials lie ahead, the method demonstrates the practical value of AI in protein design. How will this tool influence the development of drugs for complex targets?
