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Alzheimer's disease (AD) is an uncurable progressive neurodegenerative disease and is the most common cause of dementia. As current understanding of the disease suggests damage begins accumulating a decade before diagnosable symptoms, preventative treatment strategies will require screenings during the asymptomatic state. The high cost of PET and MRI scans make them challenging for the throughput necessary to screen the large population of 65+ individuals most at risk of developing AD. An alternative is near-IR fluorescence imaging, which is less costly and less invasive. We have reported a small-molecule fluorescent sensor able to selectively detect and oxidize the amyloid-β oligomers and fibrils implicated as pathogenic agents in the early development of AD. In this study, we use computational modeling to gain insights into what changes in sensor-protein binding lead to both turn-on fluorescence and turn-on singlet oxygen generation. We utilize molecular dynamics to model sensor behavior in multiple environments, including sensor complexation and protein binding. Both density functional theory (DFT) and time-dependent DFT ab initio calculations are used to monitor intra- and inter-molecular photophysical properties of the molecule. Results show that the structural dynamics of the sensor depends on its binding environment and that the structural changes upon binding are correlated with changes in sensor photophysical characteristics. This investigation contributes to a better understanding of how molecular design gives rise to desirable properties for molecular sensing, leading to improved ability to rationally design near-IR fluorescent sensors for AD.