The zero-dipole summation (ZD) method recently developed as one of the non-Ewald methods was extensively applied to a molecular dynamics (MD) simulation of a large biomolecular system, composed of a membrane protein with explicit water and lipid molecules. As in our previous report for a homogeneous water system, the ZD method reproduced the electrostatic energies of the current protein system, which were very similar to those generated by the Ewald method. The MD simulations using the ZD method provided a stable molecular system, with similar structures and dynamic properties to those produced by the conventional Particle mesh Ewald method. (C) 2013 Elsevier B.V. All rights reserved.