hydrogen-bond acceptors

A hydrogen-bond acceptor is the partner on the receiving end of a hydrogen bond: an atom with a lone pair of electrons that welcomes a hydrogen offered by a donor. In drug molecules these are typically nitrogen and oxygen atoms, such as the oxygen of a carbonyl, an ether, or a ring nitrogen. If a donor is an outstretched hand, an acceptor is the open hand waiting to be clasped.

Like donors, acceptors are counted as a fast property of the structure. Each one is a polar contact point that holds onto water and adds to a molecule's overall polarity, so a high acceptor count, like a large polar surface area, tends to slow permeability. Lipinski's rule of five sets a soft ceiling of ten acceptors.

Different counting conventions exist (some count every nitrogen and oxygen; others count only those genuinely capable of accepting), so the exact number can vary between software tools. As with donors, acceptors that make strong, well-placed hydrogen bonds to the target are valuable, while gratuitous ones simply cost permeability.