Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE)

Liu, Shu; Fu, Rao; Cheng, Xiao; Chen, Sheng-Ping; Zhou, Li-Hua

doi:10.1186/1472-6807-12-21

BMC Structural Biology

Table 3 The RMSD values of three alignment protocols

From: Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE)

Compound Number	Pdb ID	Ligand	RMSD(Å)^a	RMSD(Å)^b	RMSD(Å)^c	pIC₅₀^d	pIC₅₀^e	pIC₅₀^f
1	1 W51	L01	0.36	0.36	0.645	6.7	7.337	6.72
2	1TQF	32P	0.328	0.409	3.608	5.857	8.627	8.23
3	1YM2	AUA	0.38	0.348	0.95	8.0	7.617	8.34
4	1YM4	AMK	0.305	0.485	2.24	7.41	7.74	7.38
5	2B8V	3BN	0.416	0.47	1.739	7.01	7.27	7.28
6	2F3E	AXQ	0.27	0.242	0.676	6.81	7.23	7.26
7	2F3F	AXF	0.27	0.344	1.445	6.72	6.69	6.98
8	2IQG	F2I	0.398	0.404	0.846	8.3	7.72	7.55
9	2IRZ	I02	0.401	0.354	2.219	7.92	8.08	7.24
10	2IS0	I03	0.483	0.556	2.184	6.7	8.05	7.42
11	2OAH	QIN	0.857	0.525	2.145	7.96	7.7	7.61
12	2OHL	2AQ	0.144	0.192	0.08	2.7	3.51	3.01
13	2OHM	8AP	0.36	0.468	1.524	3.51	4.12	4.06
14	2OHP	6IP	0.576	0.535	2.432	4.03	4.34	4.22
15	2OHQ	7IP	0.35	0.501	1.29	4.6	5.15	4.27
16	2OHR	8IP	0.297	0.359	2.428	5.0	4.74	4.45
17	2OHS	9IP	0.256	0.314	2.438	5.4	5.06	5.33
18	2OHT	IP6	0.455	0.464	1.743	5.04	4.6	5.13
19	2OHU	IP7	0.906	0.942	1.921	5.38	5.06	4.87
20	2P83	MR0	0.345	0.363	1.903	7.96	7.54	7.28
21	2PH6	712	0.371	0.563	3.184	7.57	7.97	7.58
22	2B8L	5HA	0.316	0.433	2.51	8.0	8.12	7.72
23	2QZL	IXS	0.41	0.4	2.122	8.1	8.68	8.37
24	2ZE1	411	0.825	0.851	0.946	5.25	5.21	5.56
25	2QP8	SC7	0.355	0.342	0.652	8.15	7.61	8.13
26	2VIE	VG0	0.396	0.52	1.705	7.48	7.58	7.77
27	2VJ7	VG6	0.765	0.692	2.0	7.31	7.3	7.46
28	2VJ9	VG7	0.413	0.475	1.094	6.74	7.25	7.21
29	2VNM	CM8	0.387	0.572	2.457	8.52	8.09	8.3
30	2VNN	CM7	0.366	0.333	1.58	8.7	8.0	8.38
31	2WF0	ZY0	0.51	0.527	1.133	6.68	7.25	7.54
32	2WF1	ZY1	0.377	0.361	2.342	8.7	8.19	8.41
33	2ZDZ	310	0.871	0.901	1.642	6.15	5.57	5.95
34	2FDP	FRP	0.415	0.428	2.18	7.59	7.13	7.0
35	3CIB	314	0.343	0.355	0.558	7.85	7.58	7.99
36	3CIC	316	0.308	0.291	2.565	8.52	7.62	8.37
37	3CID	318	0.336	0.356	0.816	8.3	7.64	8.37
38	3DM6	757	0.659	0.716	2.814	7.43	8.57	7.88
39	3DUY	AFJ	0.443	0.653	1.749	5.85	6.78	6.1
40	3DV1	AR9	0.267	0.251	0.608	6.23	6.61	6.37
41	2P4J	23I	0.614	0.645	4.611	8.96	8.55	8.15
42	3FKT	SII	0.596	0.723	1.749	5.55	4.76	6.22
43	2QK5	CS5	0.405	0.392	2.416	7.7	7.63	7.99
44	1XS7	MMI	0.628	0.604	1.37	7.59	7.2	6.47
45	1FKN	OM99-2	1.262	1.56	3.3	8.8	8.58	9.03
46	1M4H	OM00-3	1.137	1.68	3.9	9.51	9.24	9.3

^aProtocol 1. The 46 co-crystallized ligands were aligned in the binding pocket of 1W51 by the superimposition method using the C_α atoms (1W51 structure as the reference). Subsequently, each BACE-1/inhibitor complex (each inhibitor and A chain of 1W51) was energy minimized using the AMBER 9.0 program.
^bProtocol 2. The 46 co-crystallized ligands were refined before translocation and energy minimization that was adopted in protocol 1.
^cProtocol 3. The 46 co-crystallized ligands were docked into 1W51 using the Surflex program (version 2.11), followed by the energy minimization routine mentioned above.
^dexperimental.
^epredicted with the 3-PC distance-dependent dielectric constant model (built from a single X-ray crystal structure).
^fpredicted with the 5-PC sigmoidal electrostatic model (built from the actual complexes present in the PDB).

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ISSN: 1472-6807

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