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

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

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.

• Jezik: Angleški jezik
• Ključne besede: CPANN, androgen receptor, estrogen receptor, endocrine-disrupting chemicals, endocrinology
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 15 str.
• Številčenje: Vol. 11, iss. 6, art. 486
• PID: 20.500.12556/RUL-146397
• UDK: 616.4+612.43
• ISSN pri članku: 2305-6304
• DOI: 10.3390/toxics11060486
• COBISS.SI-ID: 153712131
• Datum objave v RUL: 17.07.2023

Gradivo je del revije

• Naslov: Toxics
• Skrajšan naslov: Toxics
• Založnik: MDPI
• ISSN: 2305-6304
• COBISS.SI-ID: 520262681

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: androgeni receptor, estrogenski receptor, endokrine motnje, protipropagacijske umetne nevronske mreže, endokrinologija, hormonski motilci

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0170
• Naslov: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin