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.