How BINDI – a computer-designed protein – causes cancer cell death

BINDI UW

A small chunk of protein (red) bound to BHRF1 (grey) was extended to make a much longer protein (left). This was then designed to have a rigid folded structure (right) for tight and specific interactions with the target.

Image: UW Institute for Protein Design

A fascinating paper from the UW Institute for Protein Design was released in the scientific journal Cell last week. It described the design and development of a completely new protein which binds and inhibits cancer-causing protein BHRF1. BHRF1 is encoded by the Epstein-Barr virus (EBV) and is responsible for cell growth disruption. EBV is linked to a number of cancers including Burkitt’s lymphoma and Hodgkin’s lymphoma.

The team at IPD computer-designed and engineered the new protein BINDI from scratch. BINDI triggers self-destruction of EBV-infected cells by binding with a particular groove (BH3 if you’re interested) in BHRF1. Once it binds it’s prompts the EBV-infected cells to ‘shrivel, disassemble their components and burst into small pieces.’

Designer proteins, and as a wider subset computational biology, offers tremendous opportunities for diseases requiring targeted cell death. They can potentially be taken beyond cancer to other diseases areas which offers an advantage over currently developed ADCs. Because the proteins are designed using de novo scaffolds they could be made to target almost any disease in which binding a protein to a target results in an improved condition.

For more information on the study here are a couple of papers – one from the UW Institute for Protein Design and one from the team themselves published in UW HSNewsBeat.  

Computational biology is still most widely present in an academic setting, however it will be interesting to see how far Big Pharma and Biotech start to explore this field given BINDI’s early success. I’d be interested to hear your thoughts about this interesting field, and where you think the major opportunities might lie.

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