PharmacoMatch: Efficient 3D Pharmacophore Screening via Neural Subgraph Matching

Fuente: arXiv
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Main Authors: Rose, Daniel, Wieder, Oliver, Seidel, Thomas, Langer, Thierry
Format: Preprint
Published: 2024
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author Rose, Daniel
Wieder, Oliver
Seidel, Thomas
Langer, Thierry
author_facet Rose, Daniel
Wieder, Oliver
Seidel, Thomas
Langer, Thierry
contents The increasing size of screening libraries poses a significant challenge for the development of virtual screening methods for drug discovery, necessitating a re-evaluation of traditional approaches in the era of big data. Although 3D pharmacophore screening remains a prevalent technique, its application to very large datasets is limited by the computational cost associated with matching query pharmacophores to database molecules. In this study, we introduce PharmacoMatch, a novel contrastive learning approach based on neural subgraph matching. Our method reinterprets pharmacophore screening as an approximate subgraph matching problem and enables efficient querying of conformational databases by encoding query-target relationships in the embedding space. We conduct comprehensive investigations of the learned representations and evaluate PharmacoMatch as pre-screening tool in a zero-shot setting. We demonstrate significantly shorter runtimes and comparable performance metrics to existing solutions, providing a promising speed-up for screening very large datasets.
format Preprint
id arxiv_https___arxiv_org_abs_2409_06316
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle PharmacoMatch: Efficient 3D Pharmacophore Screening via Neural Subgraph Matching
Rose, Daniel
Wieder, Oliver
Seidel, Thomas
Langer, Thierry
Machine Learning
Artificial Intelligence
Quantitative Methods
The increasing size of screening libraries poses a significant challenge for the development of virtual screening methods for drug discovery, necessitating a re-evaluation of traditional approaches in the era of big data. Although 3D pharmacophore screening remains a prevalent technique, its application to very large datasets is limited by the computational cost associated with matching query pharmacophores to database molecules. In this study, we introduce PharmacoMatch, a novel contrastive learning approach based on neural subgraph matching. Our method reinterprets pharmacophore screening as an approximate subgraph matching problem and enables efficient querying of conformational databases by encoding query-target relationships in the embedding space. We conduct comprehensive investigations of the learned representations and evaluate PharmacoMatch as pre-screening tool in a zero-shot setting. We demonstrate significantly shorter runtimes and comparable performance metrics to existing solutions, providing a promising speed-up for screening very large datasets.
title PharmacoMatch: Efficient 3D Pharmacophore Screening via Neural Subgraph Matching
topic Machine Learning
Artificial Intelligence
Quantitative Methods
url https://arxiv.org/abs/2409.06316