Target Fisher: a Consensus Structure-Based Target Prediction Tool, and its Application in the Discovery of Selective MAO-B Inhibitors.

Autor: Fernández JF; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Heredia LM; Universidad Nacional de la Plata, CEQUINOR, ARGENTINA., Caracciolo F; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Esses D; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Suarez R; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Siless G; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Perez C; Instituto de Quimica Medica, Medicinal Chemistry, SPAIN., Rodríguez-Franco MI; Instituto de Quimica Medica, Medicinal Chemistry, SPAIN., Fernández LR; Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Organic Chemistry, ARGENTINA., Palermo JA; UMYMFOR-Facultad de Ciencias Exactas y Naturales - Universidad de Buenos Aires, Química Orgánica, Ciudad Universiaria, Pabellón 2, 1428, Buenos Aires, ARGENTINA., Lavecchia M; Universidad Nacional de la Plata, CEQUINOR, ARGENTINA.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Oct 24, pp. e202401838. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1002/chem.202401838
Abstrakt: In this work we introduce Target Fisher, a consensus structure-based target prediction tool that integrates molecular docking and machine learning with the aim to aid in the identification of potential biological targets and the optimization of the use of bioassays. Target Fisher uses per-residue energy decomposition profiles extracted from docking poses as fingerprints to train target-specific machine learning models. It provides predictions for a curated set of 37 protein targets, covering a diverse range of biological entities, and offers a user-friendly interface accessible via a web server (https://gqc.quimica.unlp.edu.ar/targetfisher/). In this sense, Target Fisher is a valuable tool to aid organic and medicinal chemistry groups in target identification, drug discovery and drug repurposing. As a case study, we demonstrate the efficacy of Target Fisher by screening a small library of assorted natural products for targets relevant to neurodegenerative diseases, which resulted in the identification and experimental validation of selective inhibitors of monoamine oxidase B (MAO-B).
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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