Predicting dual-targeting anti-influenza agents using multi-models

Yu Wang, Hu Ge, Yufang Xie, Yingyan He, Mengyan Xu, Qiong Gu* and Jun Xu*

School of Pharmaceutical Sciences & Institute of Human Virology, Sun Yat-Sen University, 132 East Circle Road at University City, Guangzhou, 510006, China.

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Supplementary Materials

Table S1 The parameters and validity of the SVM models

q2cv / MSEcv / r2test / MSEpred / C / γ / ε / Evaluation / Features
1 / 0.70 / 0.84 / 0.65 / 0.81 / 8.0 / 0.5 / 0.001 / ReliefF / SlogP_VSA8,vsa_don,PEOE_VSA-1,PEOE_VSA-5,a_nN,b_double,Jurs_FNSA_1,SMR_VSA2,Jurs_RNCS,rings
2 / 0.71 / 0.63 / 0.68 / 0.66 / 32.0 / 0.125 / 0.5 / CFS / SlogP_VSA8,SMR_VSA4,vsa_don,PEOE_VSA-1,Jurs_RNCS,density,Jurs_FNSA_3,a_nO,PEOE_VSA-5,Jurs_FNSA_2
3 / 0.68 / 0.92 / 0.64 / 0.85 / 8.0 / 0.5 / 0.5 / GFA / GCUT_SLOGP,Jurs_FNSA_1,Jurs_FNSA_2,Jurs_RNCS,PEOE_VSA-1,SMR_VSA1,SMR_VSA4,SlogP_VSA8,a_aro,vsa_don

Table S2 Definition of descriptors used for training the SVM models

Descriptor / Definition
a_aro / Number of aromatic atoms
a_nN / Number of nitrogen atoms
a_nO / Number of oxygen atoms
b_double / Number of double bonds. Aromatic bonds are not considered to be double bonds.
density / Mass mass density: weight divided by VDW volume
GCUT_SLOGP / Log P based on atomic contributions and a modified graph distance
Jurs_FNSA_1 / Sum of negative surface areas divided by total molecular solvent-accessible surface area
Jurs_FNSA_2 / Sum of negative surface areas divided by total molecular solvent-accessible surface area
Jurs_FNSA_3 / Sum of negative surface areas divided by total molecular solvent-accessible surface area
Jurs_RNCS / Relative negative charge surface area
PEOE_VSA-1 / Sum of approximate accessible VDW surface area for atom whose partial charge is in the range [-0.10,-0.05)
PEOE_VSA-5 / Sum of approximate accessible VDW surface area for atom whose partial charge is in the range [-0.30,-0.25).
rings / Number of rings
SlogP_VSA8 / Sum of approximate accessible VDW surface area for atom whose contribution to logP(o/w) lies in (0.30, 0.40]
SMR_VSA1 / Sum of approximate accessible VDW surface area for atom whose contribution to Molecular refractivity lies in (0.110,0.260]
SMR_VSA2 / Sum of approximate accessible VDW surface area for atom whose contribution to Molecular refractivity lies in (0.260,0.350]
SMR_VSA4 / Sum of approximate accessible VDW surface area for atom whose contribution to Molecular refractivity lies in (0.390,0.440]
vsa_don / Approximation to the sum of VDW surface areas of pure hydrogen bond donors

Fig. S1 The binding poses of (A) AF-399/42124337 (B) AN-655/14767002 (C) AF-399/41669482.

Fig.S2The total energy vs time for the 10ns MD in HA and NA systems.The numbers are in consistent with the compound’s ID in Table 2.

Table S3The SVM predicted activity for the top virtual hits

ID / SPECS-ID / pIC50
1 / AE-562/12222080 / 5.1280
2 / AF-399/15284080 / 5.2159
3 / AF-399/41669482 / 4.9902
4 / AF-399/42124337 / 4.7721
5 / AF-399/42309185 / 6.6042
6 / AF-399/42874517 / 5.7410
7 / AG-205/13382044 / 5.4086
8 / AG-205/14151009 / 6.6087
9 / AG-205/36732038 / 6.3478
10 / AG-690/11450800 / 5.2387
11 / AG-690/13701223 / 6.6363
12 / AG-690/33940064 / 5.1274
13 / AG-690/40699294 / 5.8974
14 / AH-487/41141211 / 5.2890
15 / AK-777/37076029 / 5.1010
16 / AN-655/14767002 / 4.2015
17 / AN-698/40847941 / 5.0689
18 / AN-698/41081576 / 4.8418
19 / AN-989/40683994 / 6.4592
20 / AO-081/41133515 / 5.1595
21 / AO-365/43113524 / 4.7055
22 / AO-365/43113526 / 4.7921
23 / AO-365/43400601 / 5.0443
24 / AP-263/43326786 / 5.4613

Fig. S3The binding modes of NA with (A) Oseltamivir (B) Zanamivir (C) AF-399/42124337.

Table S4 The enrichment factor and GH score for docking program validation

Enrichment factor / GH score
HA / NA / HA / NA
MOE / 16.6667 / 11.9333 / 0.7542 / 0.7533
CDOCKER / 0.6838 / 1.0613 / 0.0351 / 0.0744
LIGANDFIT / 3.564 / 11.2616 / 0.1418 / 0.6417
SURFLEX / 3.3333 / 0.3545 / 0.1904 / 0.0247
AUTODOCK-VINA / 0 / 0.4028 / 0 / 0.0314