The simulations in this work are conducted in vacuum, where the Flexible Topology particles are the only particles in the system. To initialize the system, we begin by randomly introducing 22 particles in a 6 by 6 by 6 Å cube. Ghost particles are inserted one at a time and trial positions are only accepted if the atom is farther than 0.4 from all system atoms and all ghost particles inserted so far. Ghost particle attributes σ , ε and q are selected randomly from the bounds in Table . The λ attributes are initialized uniformly at 0.7. The simulations are conducted using OpenMM. To create a simulation object, first empty system and topology objects are created and the ghost particles are added. To ensure adequate stability at the desired simulation conditions (a timestep of 2 fs and a temperature of 300 K), each particle is given a mass of 100 amu. A number of forces are then added to the system as described below.