SurA has prolyl-peptidyl isomerase activity and is involved in the transport and maturation of several outer membrane proteins. Loss of SurA activity has been shown to render resistant bacterial strains sensitive to antibiotics, making SurA an interesting target in combating antibiotic resistance. Our second target was the Cyclin G-associated kinase (GAK): a serine/threonine kinase, serving as a regulator of clathrin-mediated endocytosis and clathrin trafficking. GAK represents an important host factor involved in the regulation of viral entry and assembly of different RNA viruses, such as Hepatitis C, Dengue, and Ebola virus, and is of interest as an anti-viral target. Our study aims to benchmark and demonstrate the potential of ML-boosted screening with HASTEN for giga-scale applications, showcasing the speed-up, robustness, and successful recall of the majority of top-scoring compounds compared to the brute-force docking results for our two targets. We further demonstrate how large numbers of compounds that fail to dock successfully can hamper the HASTEN approach, and discuss different options to handle such 'failed' compounds, ultimately resulting in a novel screening protocol for HASTEN.