Figure 2.

Proposed common overlaps of PTX and Epo B. (A and B) Atoms shown in red represent the pharmacophore shared by the two drugs. X is a pseudoatom at the centroid of the 4-gem-dimethyl, 3-OH, 7-OH system of Epo B, as well as the corresponding groups in PTX. The average distance of X from the epoxide O of Epo B is 6.93 Å (SD = 1.18 Å) as measured in the 100 lowest-energy conformations extracted from 10 separate 100-ps molecular dynamics simulations under 10 different dielectric conditions. Displayed in blue are atoms overlapping as a result of a template-forced minimization of Epo B onto PTX. (C and D) Three-dimensional overlap of the common substituents of Epo B (carbon atoms shown in cyan) with those of docetaxel (carbon atoms shown in yellow). For both molecules, oxygen atoms are displayed in red and nitrogen atoms are displayed in blue. Functional groups have been identified in white for docetaxel and black for Epo B. The two Epo conformations presented here reflect the two potential binding modes for Epo interaction with tubulin. Binding mode I in A and C and binding mode II in B and D.