The Dual-Topology Paradigm

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 

avaw is a positive constant, and and ctJ are the usual Lennard-Jones parameters found in macromolecular force fields. The role played by the term avdw (1 — A)2 in the denominator is to eliminate the singularity of the van der Waals interaction. Introduction of this soft-core potential results in bounded derivatives of the potential energy function when A tends towards 0. 

---

In this section, we present a pseudocode for an FEP alchemical transformation based on the dual-topology paradigm. The steps followed in this algorithm, specifically (c)-(f), may be implemented independently of the core of the program that generates an ensemble of configurations at a given A state - either Monte Carlo or molecular dynamics. This is probably the simplest scheme, which may be improved in several ways, as will be discussed in Sect. 2.9. 

---