While the GA+Filter+SA results are encouraging they do involve the docking of 400,000 compounds and the question whether equally good results can obtained by simply screening a library of molecules of similar size. To answer this question we dock all 250,000 molecules in the ZINC subset from which we sample the initial population for the GA searches. This approach identifies significantly more molecules with better docking scores than known binders, with the exception of CM, where the conventional HTVS approach only identifies 60 compounds compared to 511 with GA+Filter+SA (Table ). However, the known binders for the remaining targets have relatively low docking scores of less than -7.0. In the case of β 2 AR and DDR1 the GA+Filter+SA approach finds significantly more molecules with docking scores lower than -9.0 and -10.0. Here, GA+Filter+SA finds 1.9 times as many molecules with a docking score lower than -9.0 by docking only 1.6 times as many molecules. Overall, the number of molecules deemed synthetically accessible by Molecule.one is about the same as for GA+Filter+SA: somewhat higher for β 2 AR and BCD and somewhat lower for CM and DDR1 (Table , the top-10 scoring molecules for each target is shown in Figure ). The GA+Filter+SA therefore seems like a promising approach for finding molecules with very good docking scores compared to conventional HTVS of libraries.