PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion.
Year: 2025
Type: preprint
Abstract: , an inference-time multi-objective guidance algorithm that balances exploration and exploitation to iteratively refine Pareto-optimal sequences. MCTG integrates classifier-based rewards with search-tree expansion, overcoming gradient estimation challenges and data sparsity. Using PepTune, we generate diverse, chemically-modified peptides simultaneously optimized for multiple therapeutic properties, including target binding affinity, membrane permeability, solubility, hemolysis, and non-fouling for various disease-relevant targets. In total, our results demonstrate that MCTG for masked discrete diffusion is a powerful and modular approach for multi-objective sequence design in discrete state spaces.
Source: PubMed
Authors: Sophia Tang, Yinuo Zhang, Pranam Chatterjee
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W4406964179