Journal of Chemistry

Research Article

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

Table 7

Thermodynamics of binding of selected C. sanguinolenta alkaloid-PfDHODH complexes formed from docked poses obtained at both teriflunomide and FMN binding sites for the entire 50 ns simulation as well as the last 15 ns.


PL complex	Thermodynamics (kJmol^-1)
	ΔE_vdW	ΔE_elec	ΔG_PB	ΔG_SASA	ΔG_bind

PfDHODH (SBD)
Biscryptolepine⁺	−98.88	−2.98	12.41	−11.93	−101.38
Cryptoheptine	−121.99	−15.98	62.74	−14.62	−89.85
Cryptolepinone	−128.36	−14.71	72.05	−15.01	−86.03
Cryptolepine	−128.64	114.06	76.74	−14.73	47.43
Isocryptolepine	−119.75	136.18	44.06	−14.08	46.41
Neocryptolepine	−25.20	−18.23	79.23	−3.58	32.22
Hydroxycryptolepine	−135.01	130.41	83.98	−15.32	64.06

PfDHODH (SBD)
Biscryptolepine	−104.57	−4.34	−21.13	−12.58	−142.63
Cryptoheptine	−124.54	−9.08	−4.69	−14.90	−153.21
Cryptolepinone	−125.11	−13.79	−6.69	−14.96	−160.54
Cryptolepine	−129.57	106.76	−21.77	−14.92	−59.50
Isocryptolepine	−108.87	132.04	−17.91	−13.62	−8.36
Neocryptolepine	−16.63	39.93	−16.06	−1.79	5.46
Hydroxycryptolepine	−134.24	131.03	5.45	−15.19	−12.95

PfDHODH (IBD)
Biscryptolepine	−97.98	−4.02	−3.82	−12.17	−117.99
Cryptoheptine	−154.15	−18.07	72.36	−15.42	−115.28
Cryptolepinone	−171.70	−4.20	79.17	−15.36	−112.09
Cryptolepine	−148.75	101.87	89.32	−15.01	27.43
Isocryptolepine	−145.71	78.66	78.66	−15.34	26.02
Neocryptolepine	−151.33	157.30	78.48	−15.81	68.65
Hydroxycryptolepine	−161.55	98.70	87.58	−15.43	9.31

PfDHODH (IBD)
Biscryptolepine	−122.75	−9.00	−7.02	−14.74	−153.51
Cryptoheptine	−156.64	−15.77	−13.15	−15.54	−201.10
Cryptolepinone	−179.19	−5.54	30.01	−15.04	−169.77
Cryptolepine	−145.377	81.05	9.85	−14.72	−69.19
Isocryptolepine	−146.48	90.62	−18.34	−15.36	−89.56
Neocryptolepine	−149.65	142.74	−5.79	−15.90	−28.61
Hydroxycryptolepine	−160.85	90.64	−17.83	−15.58	−103.62

PL, protein-ligand.MMPBSA estimation of binding free energies using the last 15 ns (frames 3500–5000) of the MD trajectories. ⁺Biscryptolepine did not dock at the SBD; thus, estimated thermodynamic parameters should be regarded as a negative control case and, hitherto, as an additional PfDHODH IBD binding free energy estimate.