Figure 7.

Representive configurations of betulinic acid and the metalloproteinase BaP1 corresponding to extreme points in the free energy plot. (A) Conformation of betulinic acid bound to BaP1 associated with the global free-energy minimum A, where both carboxylate oxygens make contact with the Zn${}^{2+}$ ion. (AB) Local free-energy maximum AB, where only one carboxylate oxygen is in contact with the Zn${}^{2+}$ ion, but there is insufficient space for the second oxygen to engage in other strong interactions. (B) Conformation associated with free-energy minimum B, where one carboxylate oxygen makes contact with the Zn${}^{2+}$ ion, while the other is hydrogen bonded to the Arg110. (BC) Local free-energy maximum BC, where the carboxylate is no longer in contact with the Zn${}^{2+}$ ion, but there is insufficient space for solvent between the two. (C) Conformation associated with free-energy minimum C, where the carboxylate and Zn${}^{2+}$ ion are bridged by a water molecule.