Figure 7.
The S1-pocket of trypsin is shown with MacKerell’s FragMaps of benzene (purple), propane (green), hydrogen-bond donor (blue) and acceptor (red). Crystallographic poses of four inhibitors are overlaid (A–D) with the maps; polar hydrogens are shown. The benzene/propane FragMaps overlap the central aromatic rings of all the inhibitors (purple arrows). A critical recognition element is the hydrogen bonding between trypsin’s Asp189 and positively charged groups in the inhibitors; it is captured in the hydrogen-bond donor FragMap (blue arrows). The last inhibitor in (D) places an acid group in an appropriate position in the hydrogen-bond acceptor FragMap. The units of the LGFE and experimental binding affinities are in kcal/mol. This is Figure 2 from reference 38.