Accounting for receptor flexibility is a major challenge for P-L scoring since conformational changes of proteins can range from small rearrangements of side chains to large movements of whole domains . Molecular Dynamics (MD) simulations can sample the dynamic behavior of P-L complexes, allowing for computation of the free energy and the kinetics of ligand binding, but they are cumbersome and hard to apply in high-throughput mode . Moreover, potential/free energy surfaces of P-L complexes contain a large number of local minima, separated from each other only by small barriers. The utilization of a higher number of P-L conformations as starting geometries allows for the evaluation of many microstates with shorter MD and decreases the cost of the optimization calculations.