Faculty, Staff and Student Publications

Language

English

Publication Date

4-7-2025

Journal

Communications Chemistry

DOI

10.1038/s42004-025-01506-1

PMID

40195508

PMCID

PMC11977223

PubMedCentral® Posted Date

4-7-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Accurate protein-ligand binding affinity prediction is crucial in drug discovery. Existing methods are predominately docking-free, without explicitly considering atom-level interaction between proteins and ligands in scenarios where crystallized protein-ligand binding conformations are unavailable. Now, with breakthroughs in deep learning AI-based protein folding and binding conformation prediction, can we improve binding affinity prediction? This study introduces a framework, Folding-Docking-Affinity (FDA), which folds proteins, determines protein-ligand binding conformations, and predicts binding affinities from three-dimensional protein-ligand binding structures. Our experimental results indicate that FDA performs comparably to state-of-the-art docking-free methods. We anticipate that our proposed framework serves as a starting point for integrating binding structures for more accurate binding affinity prediction.

Keywords

Molecular modelling, Computational chemistry, Cheminformatics

Published Open-Access

yes

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