The SIMPL2 technology, developed by a group of researchers at the University of Toronto, simplifies detection and increases measurement precision, revolutionizing the study of protein-protein interactions.
Protein interactions are important in biological processes, including those that lead to illness. In order to maximize researchers’ capacity to assess protein-protein interactions for targeted pharmacological therapies, the SIMPL2 platform was created by the team behind it. The platform solves this problem by making it easier to quantify protein-protein interactions, which advances our knowledge of the kinds of chemicals required to regulate them. Previously, protein-protein interactions were thought to be “undruggable” using tiny molecules.
Many methods have been developed to measure interactions between proteins, especially more recently as the significance of protein interactions in disease has become more apparent,
However, all of these methods have shortcomings, including high costs and complicated procedures that delay results. The biggest advantages of our SIMPL2 platform are that it produces more reliable measurements and is comparatively cheaper to use.
Zhong Yao
Their findings were published in the journal Molecular Systems Biology.
While creating the first SIMPL (Split-Intein Medicated Protein Ligation) device, Yao began research on the measurement challenge of protein interactions. The split luciferase enzyme is used in SIMPL2, an update of SIMPL, to detect protein interactions by light. The entire measurement process is carried out through a single medium, which is liquid, and it also enhances interaction identification. By lowering the number of steps needed to perform measurements, this greatly streamlines the procedure.
One of the issues with SIMPL was that we had to use an additional process, called ELISA, to identify the proteins spliced by the SIMPL platform,
It was a painful process that made an otherwise effective technology more complicated and expensive to use than it needed to be. SIMPL2 only requires one step, which can be performed manually, or it can be automated for even more efficiency in high-throughput studies.
Zhong Yao
The study team measured the interactions between proteins impacted by modulators in order to assess the novel platform’s sensitivity and suitability. Among the compounds known as protein modulators are those that promote protein-protein interactions, inhibit protein-protein interactions, and aid in the breakdown of target proteins. Even in situations where the interactions were weak, SIMPL2 was proven to be effective at detecting them.
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Although AI and quantum computing have simplified the process of designing tiny molecules for medicinal therapy, this has resulted in the need for far quicker techniques to verify the effectiveness of novel medications. That need can be satisfied by SIMPL2, which can be used to assess how novel compounds interact with their target proteins in human cells that have been grown. Additionally, it can keep up with the speed at which new molecules are being created.
We designed SIMPL2 to be a universal method for studying protein interactions that is rapid and inexpensive, as well as highly sensitive,
Now that we have optimized the platform, our next step is to use it to study interactions that play key roles in diseases, like cancer, to learn how to develop drug therapies. This work will involve the use of quantum computers and AI in collaboration with Alán Aspuru-Guzik’s lab at U of T and Insilico Medicine, a global leader in generative AI drug discovery.
Igor Stagljar
Source: Donnelly Centre – News
Journal Reference: Yao, Zhong et al. “A split intein and split luciferase-coupled system for detecting protein-protein interactions.” Molecular systems biology, 10.1038/s44320-024-00081-2. 12 Dec. 2024, DOI:10.1038/s44320-024-00081-2
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