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

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

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.

• Language: English
• Keywords: CPANN, androgen receptor, estrogen receptor, endocrine-disrupting chemicals, endocrinology
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 15 str.
• Numbering: Vol. 11, iss. 6, art. 486
• PID: 20.500.12556/RUL-146397
• UDC: 616.4+612.43
• ISSN on article: 2305-6304
• DOI: 10.3390/toxics11060486
• COBISS.SI-ID: 153712131
• Publication date in RUL: 17.07.2023

Record is a part of a journal

• Title: Toxics : Elektronski vir
• Shortened title: Toxics
• Publisher: MDPI
• ISSN: 2305-6304
• COBISS.SI-ID: 520262681

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: androgeni receptor, estrogenski receptor, endokrine motnje, protipropagacijske umetne nevronske mreže, endokrinologija, hormonski motilci

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin