Molecular dynamics simulations offer a unique tool to study chemical and biological processes at the microscopic level. Usually one has to make a choice between an all-atom (AA) model that is accurate but limited in the spatial and temporal scales that can be affordably simulated, and a coarse-grained (CG) model that is less accurate but can be used to simulate large systems for longer times. Unfortunately, this dichotomy renders some problems currently intractable. Therefore, we developed a hybrid approach where an AA solute is coupled with a CG solvent model. This novel method is a unique and complementary biophysical technique and can be used to study important chemical and biological problems. The hybrid AA/CG model is straightforward to use and was benchmarked on the membrane transfer of amino acid analogs, membrane partition coefficients of small molecules and the stability of transmembrane helices. Here, we present the latest work with the AA/CG model on partition coefficient of small molecules and protein dynamics. We also present our results in the SAMPL5 blind challenge and outline future directions.