In silico investigation of agonist activity of a structurally diverse set of drugs to hPXR using HM-BSM and HM-PNN / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences)
;
(6): 463-468, 2016.
Article
in English
| WPRIM
| ID: wpr-285245
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Computer Simulation
/
Receptors, Steroid
/
Chemistry
/
Models, Statistical
/
Neural Networks, Computer
/
Quantitative Structure-Activity Relationship
/
Small Molecule Libraries
/
Static Electricity
/
Molecular Weight
Type of study:
Prognostic study
/
Risk factors
Limits:
Humans
Language:
English
Journal:
Journal of Huazhong University of Science and Technology (Medical Sciences)
Year:
2016
Type:
Article
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