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Affinities and Kinetics Detection of Protein–Small Molecule Interactions with a Monolayer MoS2-Based Optical Imaging Platform

Hao Zhu,Zixuan Chen,Yun Chen,Jun-Jie Zhu

Quantifying the binding kinetics and affinities of protein–small molecule interactions is critical for biomarker validation, drug discovery, and deep understanding of various biological processes at the molecular-scale. Novel approaches are demanded as most common label-free techniques are mass-sensitive, which are not suitable for the detection of small molecule interactions. Here, an optical imaging platform is developed to measure the binding kinetics of both protein–small molecules and protein–ions based on monolayer MoS 2 , an ultra-thin 2D material whose optical absorption is extremely sensitive to charge. A model is established to calibrate the optical response due to the charged analyte binding and it is applied to quantify the interactions between abl1 kinase and different small-molecule inhibitors. Such a presented method is capable of distinguishing different inhibitors binding to a wild or mutated kinase, which provides guidance for drug evaluation and drug mechanism exploration. The binding kinetics of calcium ions to calmodulin is also measured, further broadening the application field of the method. In addition, the imaging capability allows mapping the local binding kinetics of the molecular interactions with a high resolution, which reveals visible spatial variability and offers a promising tool for studying heterogeneous local interfacial interactions.