where only one set of target features F T,i in a (possibly large) set ( ) is used to determine L and an offset for each target (ς i ) can be used to balance their relative probabilities. For instance, if we are running a long simulation, or a large ensemble of simulations, ς i could be progressively increased for each frame that ligand is correctly assembled. This would discourage repeated assembly of the same ligands and result in a more diverse ensemble of hits. A practical challenge to overcome is handling mismatches in the numbers of atoms between ligands. The total number of ghost particles needs to be larger or equal to the number of atoms in the largest ligand in . To match smaller ligands, the λ values of the unmatched atoms should go to zero. The value with which unmatched atoms contribute to the loss for a given ligand should be non-zero, and tuned empirically to ensure sampling is as even as possible across all ligand sizes.