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4D-QSAR studies of CB2 cannabinoid receptor inverse agonists: a comparison to 3D-QSAR

  • Houpan Zhang
  • Qiaoli Lv
  • Weidong Xu
  • Xiaoping Lai
  • Ya Liu
  • Guogang TuEmail author
Original Research

Abstract

Over the years QSAR methods have developed from 2D-QSAR to more complex 4D-QSAR which features freedom of alignment and conformational flexibility of individual ligands. This approach takes advantage of conformational ensemble profile (CEP) generated for individual compounds by molecular dynamics simulations. In present study, the 4D-QSAR methods called LQTAgrid-QSAR has been performed on a series of potent CB2 cannabinoid receptor inverse agonists. Step-wise method was used to select the most informative variables. Partial least squares (PLS) and multiple linear regression (MLR) methods were used for constructing the regression models. Y-randomization and leave-N-out cross-validation (LNO) were carried out to verify the robustness of the model and to analysis of the independent test set. Best 4D-QSAR model provided the following statistics: R2 = 0.862, q2LOO = 0.737, q2LNO = 0.719, R2Pred = 0.884 (PLS) and R2 = 0.863, q2LOO = 0.771, q2LNO = 0.761, R2Pred = 0.877 (MLR). The comparison of the 4D-QSAR to 3D-QSAR was performed.

Keywords

4D-QSAR 3D-QSAR Molecular dynamic simulation CB2 inverse agonists 

Notes

Acknowledgements

The project was supported by the Jiangxi Province Science Foundation (20171BAB205104), the graduate innovation fund of Jiangxi Province (CX2016298).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2303_MOESM1_ESM.doc (542 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicinal Chemistry, School of Pharmaceutical ScienceNanChang UniversityNanchangChina
  2. 2.Department of Science and Education, JiangXi Key Laboratory of Translational Cancer ResearchJiangXi Cancer HospitalNanchangChina

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