Potential Pitfalls with Free Energy Calculations

6 Potential Pitfalls with Free Energy Calculations 

There are two major sources of error associated with the calculation of free energies from computer simulations. Errors may arise from inaccuracies in the Hamiltonian, be it the potential model chosen or its implementation (the treatment of long-range forces, etc.) The second source of error arises from an insufficient sampling of phase space. 

The alternative to the single-topology representation is the dual-topology method. Here, both the molecular topologies are maintained during the entire simulation, such that both species exist (in a topological sense) but do not interact with each other. The Hamiltonian that describes the interaction between these groups and the environment can be described in a number of ways, the simplest of which is the linear relationship  

Many free energy calculations involve the creation or annihilation of atoms. A potential problem with such simulations is that a singularity may occur in the function for which 

Fig 1114. Comparison of scaled and unsealed Lennard-Jones potentials (Equation (11 31)) for the case where a particle disappears at A = 0 As A decreases the curves get progressively closer to the x axis 

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