This updated protocol runs on DS2.0 (PLP615) using the existing Ludi program for de novo drug design in an automated manner. Given a scaffold positioned in a protein site, Ludi is utilized to identify fragments that may be covalently fused to the scaffold and produces a collection of molecules with high Ludi scores. The nature of fragment selection and construction of new molecules depends on the mode. Finally all new compounds will be further refined using CHARMm and scored by MM-PBSA/GBSA. Please note that it is not officially supported by our R&D.