The Single-Topology Paradigm

In this section, as well as the next, we shall discuss how in silico transformations can be carried out in practice. The stratification scheme, as described in Sect. 2.6, is almost always required. Two approaches have been devised for this purpose, in which the reference, target and all intermediate states are described by either a unique topology, or two separate topologies. 

stands for the net atomic charge borne by atom i. R 3 and sl3 are the van der Waals parameters for the pair of atoms, j and the superscripts (1) and (0) refer, respectively, to the target and the reference states. Clearly, this is just one example of how modifications of the Hamiltonian can be handled. To optimize performance of FEP simulations, one might use several order parameters in 

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In sharp contrast with the single-topology paradigm, the topologies of the reference, 0, and the target, 1, states coexist in the dual-topology scheme throughout the... 

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