To conduct static hotspot scanning, each system's apo-structure is prepared using the 'protein preparation wizard' in Maestro (Schrodinger, LLC). This involved adding bond orders and formal charges to hetero groups and hydrogens to all atoms. The structure is refined, and the hydrogen bond network optimized using the OPLSe force field. Docking of the probes library is performed on the protein structure grid for each system using the standard precision (SP) mode as per Glide docking modules of the Maestro 12.6.144 software (Schrodinger, LLC, New York, NY, USA), and Ligprep (Schrodinger, LLC). 39