Exploring QSARs of the interaction of flavonoids with GABA (A) receptor using MLR, ANN and SVM techniques

Figures & data

Table 1. List of 78 flavoniods and their observed, estimated log K_i values (MLR) with their residuals.

Compd. No.	Compound	Obs. log Ki	Est. log Ki MLR	Residual MLR
Training set
3	6-Chloro-4′-methoxyflavonc	0.097	0.367	−0.270
4	6-Bromo-4′-methoxyflavone	0.322	0.449	−0.127
6	6-Bromo-2′-fluoroflavone	−0.424	0.186	−0.610
7	6,3′-Difluoroflavone	−0.036	0.186	−0.222
8	6-Chloro-3′-fluoroflavone	−0.932	−0.734	−0.198
9	6-Bromo-3′-fluoroflavone	−1.377	−1.231	−0.146
10	4′-Fluoroflavonc	0.556	0.304	0.252
12	6-Chloro-4′-fluoroflavone	−0.742	−0.901	0.159
13	3′-Chloroflavone	−0.212	−0.262	0.050
14	6,3′-Dichloroflavone	−1.638	−1.367	−0.271
15	3′-Bromoflavone	−0.384	−0.553	0.169
16	6-Fluoro-3′-bromoflavone	−0.627	−0.688	0.061
17	6-Chloro-3′-bromoflavone	−1.638	−1.673	0.035
19	6-Bromo-4′-nitroflavone	−0.699	−0.382	−0.317
20	6-Bromoflavone	−1.155	−1.379	0.224
21	6-Chloroflavone	−0.785	−0.806	0.021
23	6-Methoxyllavone	−0.066	0.412	−0.478
24	6-Fluoroflavone	0.653	0.176	0.477
25	6-Bromo-3′-nitroflavone	−3.000	−2.418	−0.582
26	6-Methyl-3′-nitroflavone	−2.252	−2.131	−0.121
27	6-Chloro-3′-nitroflavone	−2.097	−2.285	0.188
29	6-Fluoro-3′-nitroflavone	−0.745	−0.911	0.166
30	3′-Nitroflavonc	−0.545	−0.582	0.037
31	6-Methyl-3′-bromoflavone	−1.886	−1.523	−0.363
32	6-Nitro-3′-bromoflavone	−1.602	−1.658	0.056
33	6-Hydroxy-3′-bromoflavone	0.000	−0.539	0.539
34	6-Methoxy-3′-bromoflavone	0.000	−0.066	0.066
35	6-3′-Dimethylflavone	−0.682	−0.634	−0.048
36	3′-Methylflavone	1.000	0.332	0.668
37	5,2′-Dihydroxy-6,7,8,6′-tetramethoxy flavone	−0.444	0.061	−0.505
38	5,7,2′-Trihydroxy-6,8-dimethoxyflavone	−2.215	−1.650	−0.565
39	2′-Hydroxy-a-napthoflavone	−1.569	−1.452	−0.117
42	5,7,2′-Trihydroxyflavone	−1.125	−0.354	−0.771
44	5,7-Dihydroxy-6,8-dimethoxyflavone	−0.699	−1.776	1.077
47	5,7-Dihydroxy-8-methoxyflavone	0.182	0.037	0.145
48	6-F-Hydroxyflavone	0.422	0.230	0.192
49	7-Hydroxyflavone	0.623	0.561	0.062
50	5,6,7-Trihydroxyflavone	0.747	1.264	−0.517
51	6-Hydroxy-2′-mcthoxytlavone	0.976	1.163	−0.187
54	Flavone	0.000	0.416	−0.416
55	5,7-Dihydroxyflavone	0.477	0.828	−0.351
56	5,3′,4′-Trihydroxy-6,7-dimethoxyflavone	2.301	1.649	0.652
57	5,4′-Dihydroxy-6,7-dimcthoxyflavone	1.362	1.216	0.146
59	5,7-Dihydroxy-2′-chloroflavone	0.903	0.519	0.384
61	5,7-Dihydroxy-6,8-dibromoflavone	−0.155	0.158	−0.313
62	5,7,4′-Trihydroxyflavone	0.602	1.059	−0.457
63	3,5,7,4′-Tetrahydroxytlavone	1.969	1.356	0.613
64	5-Hydroxy-7-methoxyllavone	1.699	1.448	0.251
66	6-Fluoro,3′-hydroxyflavone	0.400	0.162	0.238
67	6-Chloro,3′-hydroxyflavone	−0.070	−0.337	0.267
69	6-Bromo-2′-nitrotlavone	−0.680	−1.359	0.679
70	6-Nitro-4′-bromollavone	−1.600	−1.829	0.229
73	3′-Fluoroflavone	0.550	0.386	0.164
74	6-Bromo-4′-fluoroflavone	−0.939	−1.470	0.531
75	6-Fluoro-3′-chlorollavone	−0.701	−0.421	−0.280
76	6-Bromo-3′-chlorollavone	−1.770	−1.637	−0.133
77	6-Methylflavone	−0.903	−0.853	−0.050
78	6-Bromo-3′-methylflavone	−0.812	−0.428	−0.384
Test set
1	6-F-luoro-3′-methoxyflavone	0.398	0.843	−0.445
2	6-Bromo-3′-mcthoxyflavone	−0.215	0.247	−0.462
5	6-Chloro-2′-fluoroflavone	−0.380	−1.714	1.334
11	6,4′-Difluoroflavone	0.398	0.025	0.373
18	6,3′-Dibromollavone	−1.721	−2.01	0.289
22	6-Nitroflavone	−0.561	−0.288	−0.273
28	6-3′-Dinitroflavone	−1.585	−1.592	0.007
40	6,2′-Dihydroxyflavone	−1.469	−0.422	−1.047
41	5,7,2′-Trihydroxy-b.-methoxyflavone	−1.420	−0.45	−0.970
43	2′-Hydroxyflavone	−0.678	−1.016	0.338
45	7,2′-Dihydroxyflavone	−0.252	−0.234	−0.018
46	5,7-Dihydroxy-6-methoxyflavone	−0.051	−0.015	0.066
52	2′-Methoxyflavone	1.508	1.427	0.081
53	2′-Amino-6-methoxyflavone	0.544	0.191	0.353
58	5,7,4′-Trihydroxy-6-mcthoxyflavone	0.000	0.056	−0.056
60	5,7-Dihydroxy-2′-fluoroflavone	0.903	1.099	−0.196
65	5,7-Dihydroxy-6,8-diiodollavone	0.000	−0.281	0.281
68	6-Bromo,3′-hydroxyflavone	−0.220	−0.926	0.706
71	3′-Methoxyflavone	0.380	0.918	−0.538
72	6-Chloro-3′-methoxyflavone	−0.072	0.401	−0.473

Figure 1. Correlation between observed and estimated log K_i for the best MLR model.

Table 2. A brief description of the selected descriptors in the MLR model.

No.	Symbol	Descriptor type	Meaning
1	MSD	Topological	Mean Square Index (Balaban)
2	PJI2	Topological	2D Petitjean Shape Index
3	IVDE	Information	Mean information content on the vertex degree equality
4	MATS8v	2D-Autocorrelation	Moran auto correlation –lag 8/weighted by atomic van der waals volumes
5	MATS2e	2D-Autocorrelation	Moran auto correlation –lag 2/weighted by atomic Sandersons electronegativities
6	GATS8e	2D-Autocorrelation	Geary auto correlation –lag 8/weighted by atomic Sandersons electronegativities
7	JGI9	Topological charge	Mean topological charge index of order 9
8	L/Bw	WHIM	length to breadth ratio by WHIM
9	R4e+	GETAWAY	R maximal auto correlation of lag 4/weighted by atomic sanderson electronegativities
10	nRORPh	Functional group counts	number of ethers

Figure 2. Ridge trace for the 10-variable model. (Color version available online at: informahealthcare.com/enz)

Figure 3. VIF plot for the 10 variable model. (Color version available online at: informahealthcare.com/enz)

Figure 4. Correlation between observed and predicted log K_i for the best ANN model of the training and test sets.

Figure 5. Correlation between observed and predicted log K_i for the best SVM model of the training and test sets.

Figure 6. Residue against observed log K_i for the SVM model.