The fragment-based approach leverages the power of distributed computing to reduce a single, monolithic (and potentially intractable) calculation into a large but manageable number of subsystem calculations. This enables large-scale quantum chemistry calculations using only workstation-level resources (i.e., single-node parallelism), as the storage footprint of a given calculation is reduced to that of the largest subsystem. This is an important consideration for investigators at under-resourced institutions. The present calculations bring ligand-protein binding calculations into the realm of what can be accomplished readily on workstation resources.