In silico investigation of agonist activity of a structurally diverse set of drugs to hPXR using HM-BSM and HM-PNN.
10.1007/s11596-016-1609-4
- Author:
Yi-Ming ZHANG
1
;
Mei-Jia CHANG
2
;
Xu-Shu YANG
3
;
Xiao HAN
4
Author Information
1. School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China.
2. School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
3. School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. yangxushu@njmu.edu.cn.
4. School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. hanxiao@njmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
agonist activity;
heuristic method-Best Subset Modeling;
heuristic method-Polynomial Neural Networks;
human pregnane X receptor;
quantitative structure-activity relationship;
structural features
- MeSH:
Computer Simulation;
Humans;
Models, Statistical;
Molecular Weight;
Neural Networks (Computer);
Quantitative Structure-Activity Relationship;
Receptors, Steroid;
agonists;
chemistry;
Small Molecule Libraries;
chemistry;
Static Electricity
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2016;36(3):463-468
- CountryChina
- Language:English
-
Abstract:
The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM)-Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r (2)=0.881, q LOO (2) =0.797, q EXT (2) =0.674; for HM-PNN, r (2)=0.882, q LOO (2) =0.856, q EXT (2) =0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR.
