We propose to perform molecular‐dynamics simulations of NADH in a variety of solvent environments, and with or without protein binding partners, with the aim of uncovering how its conformational preferences govern experimentally observed shifts in fluorescence lifetime. By simulating NADH in explicit solvents spanning a range of polarities and viscosities, we will generate ensembles of its “folded” and “extended” forms and then employ hybrid quantum‐mechanical/molecular‐mechanical calculations to predict radiative and nonradiative decay rates for each dominant conformer. Comparison of these lifetimes with our multiphoton fluorescence lifetime measurements will allow us to map specific conformational populations onto distinct lifetime components, thereby establishing a first‐principles model that links structural dynamics to photophysical behavior. This will advance label-free metabolic imaging and the quantitative interpretation of FLIM data in complex biological systems. The project is funded by VR grant 2023-03787 and MSCA Postdoctoral Fellowships (101103885 ROICAM) in the group of Marica B. Ericson.