A Toolkit for the Analysis of Free-Energy Perturbation Calculations

As computational power inexorably continues to grow, harnessing the capabilities of novel processing units and architectures, free-energy calculations are progressively brought to the level of routine modeling tools for exploring the thermodynamic properties of increasingly larger molecular assemblies. Within these premises, free-energy perturbation (FEP) arguably represents the most commonly chosen approach for tackling transformations of a chemical nature between thermodynamic states. To augment the accuracy, the precision, and, hence, the reliability of these calculations, a number of good practices have been established. In the present contribution, a new toolkit, coined ParseFEP, is proposed to follow these prescriptions in a user-friendly environment. Written as a Tcl plugin, it allows FEP calculations carried out using the popular molecular-dynamics package NAMD to be analyzed seamlessly within the visualization platform VMD. The potential of the toolkit is probed through a number of illustrative examples, which demonstrate cogently how pathological cases, often related to convergence issues, can be detected and remedied by means of a pictorial approach.