Probably the biggest differences between VS and DND is in the type of guarantees they provide and the size of chemical space they can access. Since screening a given library will score all N molecules, it is guaranteed to find the best-scoring ones. However, in particular with more expensive physics-based scoring, this is limited to smaller N s. DND on the other hand has no guarantee to return the best molecules in the chemical space accessible by its molecule generator. However, because it can explore and sample chemical space in a much more focused way due to the additional optimization component, it can potentially find much higher scoring molecules, in particular those that satisfy multiple criteria.