Discovery of novel multi-functional peptides by using protein language models and graph-based deep learning

Functional peptides are one kind of short protein 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 enormous experimental efforts endeavor 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 novel method, called iMFP-LG, for identifying multi-functional peptides based on protein language models (pLMs) and graph attention networks (GATs). Comparison results showed iMFP-LG significantly outperforms state-of-the-art methods on both multifunctional 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 to 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 significant antibacterial and anticancer effect was confirmed through molecular structure alignment and biological experiments. We anticipate iMFP-LG can assist in the discovery of multi-functional peptides and contribute to the advancement of peptide drug design. Availability and implementationThe models and associated code are available at: https://github.com/chen-bioinfo/iMFP-LG. Supplementary informationSupplementary data are available online.