Free energy dual topology

Rodriguez et al. [52] determined the association free energy of DPPS in a DPPC bilayer, both in the presence and in the absence of calcium ions. They used a dual topology technique with a PC-PS hybrid, and used both thermodynamic integration and free energy perturbation to determine the free energy of DPPS association in a DPPC bilayer. They found that PS-PS association is only favorable in the presence of calcium, which has direct implications for blood coagulation. 

Hu, H., Yang, W.T. Dual-topology/dual-coordinate free-energy simulation using QM/MM force field. J. Chem. Phys. 2005,123, 041102. 

The creation or annihilation of atoms in a molecular system (e.g., in the dual topology description just discussed) is frequently applied in free energy difference calculations. Although such a process is conceptually identical to other mutations, in practice the treatment of dummy atoms in a free energy difference calculation necessitates further approximations, which cause additional problems. 

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