Drug Censorship at Scale: The Practicalities of Automation and Parallelism for Fragment Molecular Orbital (FMO) in...

Quantum mechanics (QM) methods are increasingly applied in drug discovery, with the fragment molecular orbital (FMO) approach in GAMESS enabling large-scale calculations on biomolecular systems. This chapter outlines key lessons from integrating FMO-based QM workflows into high-throughput pipelines, focusing on challenges such as input preparation (protonation, charge assignment, minimization, and truncation), error classification, and output parsing. It also highlights limitations in scaling GAMESS on modern HPC resources and offers practical guidance on designing user-friendly interfaces. The aim is to provide non-proprietary insights for researchers seeking to adopt QM methods in drug discovery.