3.4 3D-QSAR model (CoMFA and CoMSIA analysis)
Model showed good credibility with a high r2 (>0.8), high q2 (>0.4), comparatively low SEE and relatively high F values was built from the entire molecular space field and electrostatic field and it can be used to predict biological activity and visualize favorable and unfavorable characteristics. The first-rank CoMSIA model of NLRP3 (table 5) consisted of hydrophobic filed (0.692), and hydrogen bond acceptor (0.308).0.692 0.308
In CoMFA model, there is only one single factor steric field, with the proportion of the electrostatic field is 0. For the CoMFA model, the cross-validation correlation coefficient (q2) and the non-cross-validation correlation coefficient (r2) under different optimal component numbers (ONC) are both greater than 0.4 and 0.9, indicating a reliable confidence level.
We respectively superimposed CoMFA and CoMSIA contour maps on the control and TCM candidates. For CoMFA analysis of NLRP3 (Figure 17),The 17 compound and the other four candidates of the bulky rings are located in the spatially dominant area (green). And almost no large groups appear near the unpopular (yellow) Chinese medicine candidate area. After mapping the CoMFA contours, we conclude that the Chinese medicine candidate may have a higher biological activity than the control, which is consistent with the docking results. For CoMSIA analysis of NLRP3 (Figure 18),after mapping the CoMSIA contours, we conclude that the Chinese medicine candidate may have a higher biological activity than the control, which is consistent with the docking results. At the same time, it can be seen from CoMFA and CoMSIA contour maps that the number of hydrogen bonds bound to NLRP3 by the four candidates is significantly higher than that of 17 compound, which again proves that the activity of Chinese medicine candidates may be stronger than control. Partial Regression Leverage Plots of 3D-QSAR was shown in Figure 14
All in all, the CoMFA and CoMSIA models proved that the candidates not only bound with the protein, but also have excellent biological activity.