Dataset Information

GPCRLigNet: rapid screening for GPCR active ligands using machine learning.

ABSTRACT: Molecules with bioactivity towards G protein-coupled receptors represent a subset of the vast space of small drug-like molecules. Here, we compare machine learning models, including dilated graph convolutional networks, that conduct binary classification to quickly identify molecules with activity towards G protein-coupled receptors. The models are trained and validated using a large set of over 600,000 active, inactive, and decoy compounds. The best performing machine learning model, dubbed GPCRLigNet, was a surprisingly simple feedforward dense neural network mapping from Morgan fingerprints to activity. Incorporation of GPCRLigNet into a high-throughput virtual screening workflow is demonstrated with molecular docking towards a particular G protein-coupled receptor, the pituitary adenylate cyclase-activating polypeptide receptor type 1. Through rigorous comparison of docking scores for molecules selected with and without using GPCRLigNet, we demonstrate an enrichment of potentially potent molecules using GPCRLigNet. This work provides a proof of principle that GPCRLigNet can effectively hone the chemical search space towards ligands with G protein-coupled receptor activity.

SUBMITTER: Remington JM

PROVIDER: S-EPMC10379640 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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GPCRLigNet: rapid screening for GPCR active ligands using machine learning.

Remington Jacob M JM McKay Kyle T KT Beckage Noah B NB Ferrell Jonathon B JB Schneebeli Severin T ST Li Jianing J

Journal of computer-aided molecular design 20230225 3

Molecules with bioactivity towards G protein-coupled receptors represent a subset of the vast space of small drug-like molecules. Here, we compare machine learning models, including dilated graph convolutional networks, that conduct binary classification to quickly identify molecules with activity towards G protein-coupled receptors. The models are trained and validated using a large set of over 600,000 active, inactive, and decoy compounds. The best performing machine learning model, dubbed GPC ...[more]

PMID: 36840893

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GPCRLigNet: rapid screening for GPCR active ligands using machine learning.

Publications

GPCRLigNet: rapid screening for GPCR active ligands using machine learning.

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