Moreover, in constrained reaction environments such as in enzyme and nanomaterial binding sites, early evidence suggests that BD angles for reactivity can be quite distinct, since reactivity concepts assuming orbital overlaps during random collision are not directly applicable. 
For instance, the BD value determined for enzymatic cleavage of an amide by a serine protease (subtilisin) was 88°, quite distinct from the hydride-formaldehyde value of 107°; moreover, compilation of literature crystallographic BD angle values for the same reaction mediated by different protein catalysts clustered at 89 ± 7°  (i.e., only slightly offset from directly above or below the carbonyl carbon). At the same time, the subtilisin FL value was 8°, and FL angle values from the careful compilation clustered at 4 ± 6° (i.e., only slightly offset from directly behind the carbonyl; see the Flippin–Lodge angle article).