OmegAMP: Targeted AMP Discovery through Biologically Informed Generation

Fuente: arXiv
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Main Authors: Soares, Diogo, Hetzel, Leon, Szymczak, Paulina, Torres, Marcelo Der Torossian, Sommer, Johanna, de la Fuente-Nunez, Cesar, Theis, Fabian, Günnemann, Stephan, Szczurek, Ewa
Format: Preprint
Published: 2025
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author Soares, Diogo
Hetzel, Leon
Szymczak, Paulina
Torres, Marcelo Der Torossian
Sommer, Johanna
de la Fuente-Nunez, Cesar
Theis, Fabian
Günnemann, Stephan
Szczurek, Ewa
author_facet Soares, Diogo
Hetzel, Leon
Szymczak, Paulina
Torres, Marcelo Der Torossian
Sommer, Johanna
de la Fuente-Nunez, Cesar
Theis, Fabian
Günnemann, Stephan
Szczurek, Ewa
contents Deep learning-based antimicrobial peptide (AMP) discovery faces critical challenges such as limited controllability, lack of representations that efficiently model antimicrobial properties, and low experimental hit rates. To address these challenges, we introduce OmegAMP, a framework designed for reliable AMP generation with increased controllability. Its diffusion-based generative model leverages a novel conditioning mechanism to achieve fine-grained control over desired physicochemical properties and to direct generation towards specific activity profiles, including species-specific effectiveness. This is further enhanced by a biologically informed encoding space that significantly improves overall generative performance. Complementing these generative capabilities, OmegAMP leverages a novel synthetic data augmentation strategy to train classifiers for AMP filtering, drastically reducing false positive rates and thereby increasing the likelihood of experimental success. Our in silico experiments demonstrate that OmegAMP delivers state-of-the-art performance across key stages of the AMP discovery pipeline, enabling us to achieve an unprecedented success rate in wet lab experiments. We tested 25 candidate peptides, 24 of them (96%) demonstrated antimicrobial activity, proving effective even against multi-drug resistant strains. Our findings underscore OmegAMP's potential to significantly advance computational frameworks in the fight against antimicrobial resistance.
format Preprint
id arxiv_https___arxiv_org_abs_2504_17247
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle OmegAMP: Targeted AMP Discovery through Biologically Informed Generation
Soares, Diogo
Hetzel, Leon
Szymczak, Paulina
Torres, Marcelo Der Torossian
Sommer, Johanna
de la Fuente-Nunez, Cesar
Theis, Fabian
Günnemann, Stephan
Szczurek, Ewa
Machine Learning
Artificial Intelligence
Biomolecules
Deep learning-based antimicrobial peptide (AMP) discovery faces critical challenges such as limited controllability, lack of representations that efficiently model antimicrobial properties, and low experimental hit rates. To address these challenges, we introduce OmegAMP, a framework designed for reliable AMP generation with increased controllability. Its diffusion-based generative model leverages a novel conditioning mechanism to achieve fine-grained control over desired physicochemical properties and to direct generation towards specific activity profiles, including species-specific effectiveness. This is further enhanced by a biologically informed encoding space that significantly improves overall generative performance. Complementing these generative capabilities, OmegAMP leverages a novel synthetic data augmentation strategy to train classifiers for AMP filtering, drastically reducing false positive rates and thereby increasing the likelihood of experimental success. Our in silico experiments demonstrate that OmegAMP delivers state-of-the-art performance across key stages of the AMP discovery pipeline, enabling us to achieve an unprecedented success rate in wet lab experiments. We tested 25 candidate peptides, 24 of them (96%) demonstrated antimicrobial activity, proving effective even against multi-drug resistant strains. Our findings underscore OmegAMP's potential to significantly advance computational frameworks in the fight against antimicrobial resistance.
title OmegAMP: Targeted AMP Discovery through Biologically Informed Generation
topic Machine Learning
Artificial Intelligence
Biomolecules
url https://arxiv.org/abs/2504.17247