An In Silico Study of the Interactions of Alkaloids from Cryptolepis sanguinolenta with Plasmodium falciparum Dihydrofolate Reductase and Dihydroorotate Dehydrogenase

Figure 12

Binding conformation predicted from molecular docking was stable under dynamic conditions for all complexes. (a) Trajectory showing stability of protein ligand complexes. Biscryptolepine was observed to be bound strongly at the end of the quinone-binding tunnel for ∼1.5 ns. Displacement by solvent access increased RMSD (from ∼0.5 nm to 2.5 nm), however, good binding along the mouth between 2 ns and 12 ns, followed by the periphery (interface) of the waist region from 13 ns to 50 ns (average RMSD = ∼ 2.0 nm) where it bound favorably. All ligand complexes involving alkaloids of the pg class were stable throughout the simulation (average RMSD ≤0.5 nm). Interacting residues contributing to binding affinity have been colored based on b-factors (b–d). Biscryptolepine (b) interacted strongly with the alpha helical bundle, whereas cryptoheptine (c) and cryptolepinone (d) strongly interacted in the inhibitor (teriflunomide) binding domain of the quinone-binding tunnel.

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