The energy and its analytic gradient are developed for the solvation model density (SMD) combined with the fragment molecular orbital (FMO) method. The accuracy of the energy is evaluated in comparison to full results without fragmentation for a set of neutral and charged polypeptides. The accuracy of the gradient is computed in comparison to numerical gradient. The components to the solvation energy in SMD are compared to the polarizable continuum model (PCM). FMO with SMD and PCM is applied to analyze protein-ligand binding in solution. (C) 2018 Elsevier B.V. All rights reserved.