Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng

Figures & data

Figure 1.  Sequential alignment of BCL-2, BCL-XL, and MCL-1 proteins according to ClustalW with conserved homology domains.

Table 1.  The binding energies of BCL-2, BCL-XL, and MCL-1 and the experimentally known small molecules.

Template id (CID)	Docking energy (kcal/mol)
	2W3L	2YXJ	3KZ0
3965212	–6.25	–6.79	–5.93
4905081	–6.32	–5.62	–4.12
1122818	–6.43	–9.77	–5.13

Table 2.  Molecular interaction results of BCL-2, BCL-XL, and MCL-1 into Rg1, Rg3, Rh2, and Rf.

Proteins	Ginsenosides	H-bond donor	H-bond acceptor	H-bond length (Å)	Docking energy (kcal/mol)
BCL-2	Rg1	Rg1:d:LIG1:H	2W3L:A:TYR67:OH	2.062	–1.08
		Rg1:d:LIG1:H	2W3L:A:GLU95:OE1	2.202
	Rg3	2W3L:A:ARG142:HH12	Rg3: d: LIG1: O	2.239	–1.9
	Rh2	2W3L:A:ARG12:HE2	Rh2: d: LIG1: O	2.215	–4.28
		2W3L:A:THR137:HG1	Rh2: d: LIG1: O	2.166
	Rf	2W3L:A:ASN131:HD22	Rf: d: LIG1:0	1.968	–1.7
BCL-XL	Rg1	2YXJ:A:LYS:HZ1	Rg1: d: LIG1: O	2.06	–1.2
	Rg3	Rg3:d:LIG1:H	2YXJ: A: ALA142:0	2.068	–6.87
	Rh2	Rh2:d:LIG1:H	2YXJ:A:GLU153:OE1	2.228	–0.31
		2YXJ:A:THR109:HG1	Rh2: d: LIG1: O	1.183
	Rf	2YXJ:A:LYS16:HZ2	Rf: d: LIG1: O	2.127	–3.83
		2YXJ:A:LYS20:HZ2	Rf: d: LIG1: O	2.18
MCL-1	Rg1	Rg1:d:LIG1:H	3KZO: A: LEU267: O	2.011	–2.25
	Rg3	Rg3:d:LIG1:H	3KZO:A:THR266:OG1	2.183	–0.81
		3KZO:A:THR266:HG1	Rg3: d: LIG1: O	2.132
	Rh2	Rh2:d:LIG1:H	3KZO:A:GLU288:OE1	1.964	–3.25
	Rf	Rf:d:LIG1:H	3KZO:A:HIS224:ND1	2.206	–2.05

Table 3.  Average energy interactions between anti-apoptotic proteins with ginsenosides complexes.

Proteins	Ginsenosides	Total interaction energy (kcal/mol)	Total VDW interaction energy (kcal/mol)	Total electrostatic interaction energy (kcal/mol)
BCL-2	Rg1	–42.25	–40.10	–2.14
	Rg3	–6.52	–53.41	–46.89
	Rh2	–25.46	–17.09	–8.36
	Rf	–17.96	–0.96	–17.00
BCL–XL	Rg1	–24.76	–13.02	–32.86
	Rg3	–35.70	–19.15	–16.55
	Rh2	–13.80	–20.95	–7.12
	Rf	–35.87	–23.48	–17.78
MCL–1	Rg1	–94.64	–33.35	–61.28
	Rg3	–36.73	–37.05	–0.31
	Rh2	–4.84	–14.02	–18.86
	Rf	–44.79	–36.74	–8.05

Figure 2.  Illustration of docked complexes of BCL-2 (A), BCL-XL (B) and MCL-1 (C) with ginsenosides Rg1, Rg3, Rh2 and Rf.

Figure 3.  The RMSD of the twelve studied complexes to their initial structure obtained MD simulations. (A) 2W3L-ginsenosides, (B) 2YXJ-ginsenosides, (C) 3KZ0-ginsenosides.