Hierarchical Lead Optimization Pipeline

Super large-scale molecular docking (number of hundreds of millions; speed 0.1-1 second)

Energy minimization and MM-GB/SA re-scoring (number of tens of thousands; speed: minutes)

MM-PB/SA free energy calculation based on molecular dynamics (number of thousands; speed from hours to days)

Free energy perturbation (FEP)/thermodynamic integration (Ti), and Umbrella sampling (PMF) free energy calculation (number of hundreds; speed of days)