FE-ToolKit: A Versatile Software Suite for Analysis of High-Dimensional Free Energy Surfaces and Alchemical Free Energy Networks

Abstract

Free energy simulations play a pivotal role in diverse biological applications, including enzyme design, drug discovery, and biomolecular engineering. The characterization of high-dimensional free energy surfaces underlying complex enzymatic mechanisms necessitates extensive sampling through umbrella sampling or string method simulations. Accurate ranking of target-binding free energies across large ligand libraries relies on comprehensive alchemical free energy calculations organized into thermodynamic networks. The predictive accuracy of these methods hinges on robust, scalable tools for networkwide data analysis and extraction of physical properties from heterogeneous simulation data. Here, we introduce FE-ToolKit, a versatile software suite for the automated analysis of free energy surfaces, minimum free energy paths, and alchemical free energy networks (thermodynamic graphs).