2.4 3D-QSAR model (CoMFA and CoMSIA analysis)
Based on the three-dimensional structure characteristics of drug molecules and receptor molecules, 3d-qsar is a method to analyze the quantitative relationship between structure and biological activity.We divider 31 NLRP3 inhibitors with similar skeletons from Jacob Fulp’s study 40 into 25 for training set and 6 for testing set to do 3D-QSAR analysis. The 3D QSAR model was constructed using SYBYL-X 1.1. By partial least squares (PLS), we established the comparative force field analysis (CoMFA) and comparative similarity index analysis (CoMSIA) models. In order to establish appropriate 3D-QSAR model, we need to align the training set molecules, then we use atomic fitting module. Cross-validation correlation coefficient (CV) is greater than 0.4, and the model with non-cross-validation correlation coefficient (r2) greater than 0.8 is considered to be reliable. Through 3D-QSAR contour map, we can predict the biological activity of the control and Chinese medicine candidates.