Figure 10.

Comparison of the potentials of mean force (Gibbs free-energy) and the binding poses of betulin and $\beta$-boswellic acid with those of the most active compound betulinic acid. (A) Orientation of betulin associated with its free-energy minimum. The hydrophobic rings of betulin are interacting with the S1 subsite, without contact with the Zn${}^{2+}$ ion. (B) Orientation of $\beta$-boswellic acid associated with its free-energy minimum. (C) The orientation of bound betulinic acid is shown for reference. This compound fully occudes the S1${}^{\prime }$ subsite. (D) Free energy as a function of the carboxylate-Zn${}^{2+}$ ion distance for $\beta$-boswellic and betulinic acid, or hydroxyl-Zn${}^{2+}$ ion for betulin. The betulinic acid PMF is shown for comparison purposes.