This report presents molecular dynamics (MD) simulations to fill the gaps in available experimental data and provide atomistic resolution insight into the conformational dynamics of EPAC1 activation. Markov State Modelling (MSM) is a powerful approach to construct atomistic models of the energetics and kinetics of biomolecular systems. In previous work, we have combined enhanced sampling molecular dynamics with Markov State Modelling (MSM), to model changes in the protein conformational ensemble in the presence of allosteric inhibitors. However, this preceding work only covered small loop motions, rather than large domain rearrangements that characterise EPAC activity. Here we use steered molecular dynamics (sMD) to simulate the conformational change of EPAC1 from inactive to active states (and vice versa), via the intermediate state previously identified by Shao et al. These calculations were used to initiate an ensemble of unbiased MD simulations, starting from various points along the sMD coordinate. This unbiased MD dataset is subsequently used to build MSMs and coarsen the description of the conformational change to a three macrostates ("inactive", "intermediate", "active") partitioning of the EPAC1 conformational ensemble. As this methodology has only been applied to inhibitors previously, it is validated by first comparing apo WT EPAC1 to the EPAC1-cAMP complex, as well as EPAC1 L273W -cAMP. Our modelling correctly captures the activation of WT EPAC1 by cAMP, and also the prevention of the activation by the L273W mutation. Following this, we investigate the effects of I942 on EPAC1 by modelling I942 with native interactions only, as well as with additional artificial protein-ligand distance restraints to mimic hydrogen bonding interactions observed with cAMP but not I942. Comparisons of the computed con-formational ensembles allowed us to isolate and determine the effects of key cAMP-EPAC1 interactions. Finally, we propose structural modifications that could convert I942 derivatives into full EPAC1 agonists.