Fig. 2: BtuG2-CNCbl binding dynamics.
a Representative snapshot of the CNCbl-BtuG2 at the end of the 1-µs-long MD simulation performed using the BtuG2-CNCbl crystal structure. Included are the overlay of the final ligand position at the end of the unbiased (carbon atoms in blue) and the position in the crystal structure (carbon atoms in magenta). b Superposition of relaxed BtuG2 and the crystal structure. The displaced loops are annotated (cyan for the crystal structure, wheat for the relaxed structure). Arrows indicate loop movements away from the binding pocket during relaxation c COM distances between the binding pocket of the relaxed structure and the ligand initially placed arbitrarily at 8.5, 37.1 and 34.9 Å. The unbiased simulations 2 and 3 where stopped after 1 µs as CNCbl was stably bound. d Free energy profile for the binding of CNCbl to BtuG2 as a function of the COM distance between the two binding partners. The free energy of binding, i.e., the difference between the lowest energy and the energy at large COM distances, is about 20 kcal/mol. Binding positions of the CNCbl on the free energy surface are shown in magenta (A, binding pocket), in light blue (B, 12–14 Å away from binding pocket), and in green (C, 25 Å away from binding pocket). e, f The electrostatic potential map of BtuG2 is predominantly negative because of the net charge of −18e, explaining why BtuG2 attracts the positively charged or zwitterionic CNCbl/AdoCbl/Cbi molecules. The BtuG2 conformation in this figure has been obtained by removing the CNCbl from the CNCbl-bound-BtuG2 crystal structure. The colour scale ranges from −200 for the negative surface (red), to 200 for the positive surface (blue) in units of kBT/e = 26 mV at 300 K.
