Figure 5.

The so-called neighbour effect illustrated for four configurations, each marked by an inset representing the full wave function energy profile (blue) with a red diamond marking that particular configuration. The atoms involved in hydrogen bonds, namely the hydrogen donor (N48 in Arg501) and hydrogen acceptor (O15 in the amide of the ligand), show opposite behaviours to each other. The opposite behaviour between the hydrogen donor and the hydrogen acceptor is maintained once past the global minimum and entering segment 2. After transitioning the segment, the behaviour of these two atoms remains opposite to each other, but they now contribute to the whole system in a switched sense, as marked by the coloured circles shown surrounding the atoms. The green circles surrounding an atom represent increased stability (a more negative energy), while the purple circles represent decreasing stability (a less negative energy). We travel along the energy profile from left to right (i.e., the ligand moves away from the pocket). Initially, the hydrogen acceptor O15 is shown surrounded by a green circle, as its energy becomes more negative until the global minimum. When the distance increases further, away from the global minimum, segment 2 starts and the energy of O15 becomes less negative as the distance increases. Meanwhile, the hydrogen donor (N48 in Arg501) and the neighbour (carbon of the amide of the ligand) of the hydrogen acceptor show opposite behaviour. The hydrogen atom itself from the hydrogen bond can make a contribution in both senses depending on the case, although the REG value will be small and often not rank as an important contributor.