Cells interpret and record extracellular cues via dynamic rearrangements in their proteome, establishing molecular memories that guide subsequent responses. Our recent work (Dagliyan et al. 2025, under revision) uncovers a central role for extrinsic modulation of intrinsic disorder, as we term “extrinsic disorder”, as a driver of this adaptive process. Specifically, we showed that neuronal stimulation activates a phosphorylation program that toggles protein regions between ordered and disordered conformations. This complements our earlier study (Dagliyan et al. 2016, Science), in which we engineered light- and ligand-controlled proteins to trigger defined structural transitions in vitro. Here, we propose to demonstrate that phosphorylation-mediated disorder transitions constitute a proteome-wide mechanism underpinning cellular memory formation. Leveraging BioEmu (Lewis et al. 2025, Science), a state-of-the-art deep-learning framework capable of generating thousands of statistically independent protein conformations per GPU-hour, we will map equilibrium ensembles before and after stimulus-dependent phosphorylation across diverse cell types. We will apply BioEmu for each protein domain sequence with its wild type sequence, phospho-mimetic mutant, and phospho-null analogues, where stimulation dependent phosphorylation site is mutated to a negatively charged glutamic acid or to alanine that blocks phosphorylation, respectively. This approach will allow us to quantify shifts in disorder propensity and identify key regulatory nodes that encode environmental history. Successful completion will establish a unifying biophysical paradigm: extrinsic modulation of protein disorder as a fundamental mechanism by which cells encode, store, and recall molecular information. Such insights will not only deepen our understanding of cellular adaptation but also open avenues for programmable control of protein function in health and disease.