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

Figure 10

(a) Trajectory showing stability of protein ligand complexes for dm-PfDHFR. Selected starting conformations were preserved with little deviations. RMSD converged at <0.4 nm, except that of cryptoheptine (RMSD = ∼1.0 nm from 3 ns to 50 ns). A steady increase (0.4 nm–1.0 nm) in cryptolepinone RMSD was also observed between 35 ns and 50 ns, due to solvent accessibility. Interacting residues contributing to binding affinity have been colored based on b-factors (b–e). Val45, Leu46, Met55, Phe58, Ser111, and Ile112 favorably interacted with ligands of both classes, except hydroxycryptolepine (e). Hydrogen bonding with Asp54 recorded highest occupancy and residual contribution to binding (red colour; −96.60 kJol/mol), hence overall complex stability (grey to blue). Loop regions exhibited high b-factors when involved in ligand binding (b–e).

(a)

(b)

(c)

(d)

(e)