Chemical space exploration with Molpher: Generating and assessing a glucocorticoid receptor ligand library

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F24%3A43931127" target="_blank" >RIV/60461373:22310/24:43931127 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/minf.202300316" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/minf.202300316</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/minf.202300316" target="_blank" >10.1002/minf.202300316</a>

Result language

angličtina

Original language name

Chemical space exploration with Molpher: Generating and assessing a glucocorticoid receptor ligand library

Original language description

Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery of new biologically active compounds. In this study, we present a detailed analysis of the chemical library of potential glucocorticoid receptor (GR) ligands generated by the molecular generator, Molpher. To generate the targeted GR library and construct the classification models, structures from the ChEMBL database as well as from the internal IMG library, which was experimentally screened for biological activity in the primary luciferase reporter cell assay, were utilized. The composition of the targeted GR ligand library was compared with a reference library that randomly samples chemical space. A random forest model was used to determine the biological activity of ligands, incorporating its applicability domain using conformal prediction. It was demonstrated that the GR library is significantly enriched with GR ligands compared to the random library. Furthermore, a prospective analysis demonstrated that Molpher successfully designed compounds, which were subsequently experimentally confirmed to be active on the GR. A collection of 34 potential new GR ligands was also identified. Moreover, an important contribution of this study is the establishment of a comprehensive workflow for evaluating computationally generated ligands, particularly those with potential activity against targets that are challenging to dock. © 2024 The Authors. Molecular Informatics published by Wiley-VCH GmbH.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Project

<a href="/en/project/LM2023052" target="_blank" >LM2023052: National Infrastructure for Chemical Biology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Informatics

ISSN

1868-1743

e-ISSN

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Volume of the periodical

43

Issue of the periodical within the volume

8

Country of publishing house

TW - TAIWAN (PROVINCE OF CHINA)

Number of pages

24

Pages from-to

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UT code for WoS article

001268141400001

EID of the result in the Scopus database

2-s2.0-85197786625