Armed with the protocols specified here, one can integrate alchemical ABFE calculations into large scale drug discovery procedures in an ambitious manner. Using the knowledge gleaned herein on the effect of various parameters and the flexibility of the recommended protocols, it becomes possible to obtain reliable results while optimally utilising the available computational effort. Importantly, such protocols permit one to perform thousands of calculations concurrently in less than two hours allowing one to achieve the level of throughput necessary for industrial drug discovery and patient-specific therapeutic applications within the limit of available computational resources.