An efficient computational method to calculate NMR chemical shifts of large biomolecular systems is proposed. The method is based on the fragment molecular orbital (FMO) method combined with the gauge-including atomic orbital (GIAO) and continuous set of gauge transformations (CSGT) methods. It accurately reproduced the conventional ab initio NMR values for a 10-residues peptide. The method was also applied to ubiquitin (76 amino-acid residues), and the calculated chemical shifts agree well with experimentally measured shifts. The proposed method requires a much lower computational cost than the conventional ab initio methods to calculate chemical shifts of large systems. (C) 2006 Elsevier B.V. All rights reserved.