Predictive models for compound binding to androgen and estrogen receptors based on counter-propagation artificial neural networks

Mark Stanojević (Author), Marija Sollner Dolenc (Author), Marjan Vračko (Author)

Abstract

Endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with the normal function of the human endocrine system. These chemicals can affect specific nuclear receptors, such as androgen receptors (ARs) or estrogen receptors (ER) α and β, which play a crucial role in regulating complex physiological processes in humans. It is now more crucial than ever to identify EDCs and reduce exposure to them. For screening and prioritizing chemicals for further experimentation, the use of artificial neural networks (ANN), which allow the modeling of complicated, nonlinear relationships, is most appropriate. We developed six models that predict the binding of a compound to ARs, ERα, or ERβ as agonists or antagonists, using counter-propagation artificial neural networks (CPANN). Models were trained on a dataset of structurally diverse compounds, and activity data were obtained from the CompTox Chemicals Dashboard. Leave-one-out (LOO) tests were performed to validate the models. The results showed that the models had excellent performance with prediction accuracy ranging from 94% to 100%. Therefore, the models can predict the binding affinity of an unknown compound to the selected nuclear receptor based solely on its chemical structure. As such, they represent important alternatives for the safety prioritization of chemicals.

Keywords

androgeni receptor;estrogenski receptor;endokrine motnje;protipropagacijske umetne nevronske mreže;

Data

Language:	English
Year of publishing:	2023
Typology:	1.01 - Original Scientific Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	616.4+612.43
COBISS:	153712131
ISSN:	2305-6304
Views:	16
Downloads:	0
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	Endokrinologija;Hormonski motilci;
Type (COBISS):	Article
Pages:	15 str.
Volume:	ǂVol. ǂ11
Issue:	ǂiss. ǂ6, art. 486
Chronology:	2023
DOI:	10.3390/toxics11060486
ID:	19574778