iMFP-LG: Identification of Novel Multi-Functional Peptides by Using Protein Language Models and Graph-Based Deep Learning.

Functional peptides are short amino acid fragments that have a wide range of beneficial functions for living organisms. The majority of previous research focused on mono-functional peptides, but a growing number of multi-functional peptides have been discovered. Although there have been enormous experimental efforts to assay multi-functional peptides, only a small fraction of millions of known peptides have been explored. Effective and precise techniques for identifying multi-functional peptides can facilitate their discovery and mechanistic understanding. In this article, we presented a method iMFP-LG for identifying multi-functional peptides based on protein language models (pLMs) and graph attention networks (GATs). Comparison results showed that iMFP-LG outperforms state-of-the-art methods on both multi-functional bioactive peptides and multi-functional therapeutic peptides datasets. The interpretability of iMFP-LG was also illustrated by visualizing attention patterns in pLMs and GATs. Regarding the outstanding performance of iMFP-LG on the identification of multi-functional peptides, we employed iMFP-LG to screen novel candidate peptides with both ACP and AMP functions from millions of known peptides in the UniRef90. As a result, 8 candidate peptides were identified, and 1 candidate that exhibits both antibacterial and anticancer effects was confirmed through molecular structure alignment and biological experiments. We anticipate that iMFP-LG can assist in the discovery of multi-functional peptides and contribute to the advancement of peptide drug design.