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Complex-based Ligand-Binding Proteins Redesign by Equivariant Diffusion-based Generative Models

Nguyen, V. T. D.; Nguyen, N.; Hy, T. S.

2024-07-12 bioinformatics
10.1101/2024.04.17.589997 bioRxiv
Show abstract

Proteins, serving as the fundamental architects of biological processes, interact with ligands to perform a myriad of functions essential for life. Designing functional ligand-binding proteins is pivotal for advancing drug development and enhancing therapeutic efficacy. In this study, we introduce ProteinReDiff, an efficient computational framework targeting the redesign of ligand-binding proteins. Using equivariant diffusion-based generative models, ProteinReDiff enables the creation of high-affinity ligand-binding proteins without the need for detailed structural information, leveraging instead the potential of initial protein sequences and ligand SMILES strings. Our evaluations across sequence diversity, structural preservation, and ligand binding affinity underscore ProteinReDiffs potential to advance computational drug discovery and protein engineering. Our source code is publicly available at https://github.com/HySonLab/Protein_Redesign.

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