We developed a dual basis approach within the fragment molecular orbital formalism enabling efficient and accurate use of large basis sets. The method was tested on water clusters and polypeptides and applied to perform geometry optimization of chignolin (PDB: 1UAO) in solution at the level of DFT/6-31++G**, obtaining a structure in agreement with experiment (RMSD of 0.4526 angstrom). The polarization in polypeptides is discussed with a comparison of the alpha-helix and beta-strand. (C) 2014 Elsevier B.V. All rights reserved.