Figure 3.

NMR directed modeling of the ligands bound to the pore site. (A) Off-resonance NMR experiment (500 MHz) (lower line) and STD spectra (upper line) of Flutax-2 bound to microtubules (Inset) TR-NOESY spectra (mixing time, 200 ms) of Flutax-2 in the presence of microtubules (D₂O, 310 K) (a large, high-resolution version of this file is available in the Supporting Material). (B) Best model of Flutax-2 docked into the pore site. Protein residues considered in CORCEMA-ST calculations are shown in stick format. (C) Experimental STD profile of Flutax-2 bound to microtubules (black line and circles) and calculated STD profile of the best model of Flutax-2 docked into the pore site (red line and squares). (D) Average STD profile of the common protons of paclitaxel, docetaxel, and Chitax-42 (black line and circles) compared with the calculated STD profiles of cephalomannine (red line and squares), Chitax-1 (green line and squares), Chitax-17 (blue line and squares), and Chitax-4 (pink line and squares) docked into the pore site. X axis values for C and D are placed over the symbols and represent the common protons of the taxane core and/or the fluorescein moiety of Flutax-2. The order of the points has been selected so that points representing protons that are close in the graph are also close in the taxane molecule (protons not observable by STD keep its space but are not plotted). Spacing and connectivity of the points are arbitrary for presentation purposes.