Comparative Study of Factor Xa Inhibitors Using Molecular Docking/SVM/HQSAR/3D‐QSAR Methods
Jing Sun, Hai Feng Chen, Hai Rong Xia, Jian Yao, Bo Tao Fan · QSAR & Combinatorial Science · 2005
Abstract The binding modes of a group of Factor Xa (fXa) inhibitors were studied using FlexX. CoMFA, CoMSIA, HQSAR and SVM models for inhibition potency were constructed with the conformers obtained from the molecular docking. 3D‐QSAR models for oral biovailability were also constructed with the subset inhibitors. The results show that these models possess good prediction ability. The influence of substituents for the activity and oral bioavailability were explored by comparing the constructed 3D‐QSAR models. We found that some substituents have consistent effects on inhibition potency and oral bioavailablity, but some have inconsistent effects. We observed equally that the different methods involved in this study, such as molecular docking, SVM, HQSAR and 3D‐QSAR models, could be used not only for the prediction, but they are also complementary each to other. They are helpful for better understanding the interaction mechanism between inhibitors and fXa receptor.