Theoretical guiding with molecular docking for the screening of high-sensitive AIE probes for specific protein detection.

The detection of proteins is crucial in the fields of disease diagnosis and drug development. Detection of proteins by aggregation-induced emission (AIE) probes is a quick and convenient method. However, the current AIE probes for the specific protein detection mainly depended on experimental test, lacking a guiding strategy. This study presented a novel approach to design AIE probes for detecting protein using molecular docking depending on AIE luminescence mechanism of the restriction of intramolecular motions. As an example to show its feasibility, three AIE probes with pyrrolo[3,2-b]pyrrole motif were designed and synthesized. The binding of the three probes to nine common proteins were predicted in advance using the molecular docking technique, obtaining information including intermolecular forces, binding energy, and binding sites between probes with proteins. The prediction results were verified through experimental data, and the mutual comparation of experimental and molecular docking results confirmed the reliability of the information provided by the molecular docking technique. Furthermore, the probes TPPP-2Na and TPPP-4Na exhibited limit of detection as low as 0.33 μg/mL for BSA and 0.35 μg/mL for HSA, respectively. The study revealed an innovative approach for the screening and molecular design of AIE probes for the detection of proteins.