Uni-GBSA: An Automatic Workflow to Perform MM/GB(PB)SA Calculations for Virtual Screening

Evaluating the binding free energy of the protein-ligand complex is one of the most important tasks in drug design. Compared to methods like free energy perturbation (FEP) and thermodynamic integration (TI) which are accurate but resource expensive, and docking scoring functions which are less reliable but efficient, molecular mechanics/Generalized-Born (Poisson–Boltzmann) surface area (MM/GB(PB)SA), which balance accuracy and efficiency, is a good choice for evaluating binding free energy in virtual screening. There are several open-source tools for performing MM/GB(PB)SA calculations, but they are not easy to use, especially when processing a large number of molecules. Here we introduce Uni-GBSA, an automatic workflow to perform MM/GB(PB)SA calculations from force field building, structure optimization to free energy calculation. For evaluating several molecules against one protein target in virtual screening, Uni-GBSA offers a batch mode, eliminating many repeated calculations, to process the calculation for multi-molecules simultaneously and efficiently. Experiments show that Uni-GBSA with carefully designed default settings of parameters and workflow can obtain reliable binding free energy evaluation. Uni-GBSA software, including source code, is free and available at https://github.com/dptech-corp/Uni-GBSA.