iMFP-LG: Identify Novel Multi-functional Peptides Using Protein Language Models and Graph-based Deep Learning
Jiawei Luo, Kejuan Zhao, Junjie Chen, Caihua Yang, Fuchuan Qu, Yumeng Liu, Xiaopeng Jin, Ke Yan, Yang Zhang, Bin Liu
Abstract
Functional peptides are short amino acid fragments that have a wide range of beneficial functions for living organisms. The majority of previous studies have focused on mono-functional peptides, but an increasing number of multi-functional peptides have been discovered. Although there have been enormous experimental efforts to assay multi-functional peptides, only a small portion of millions of known peptides has been explored. The development of effective and accurate techniques for identifying multi-functional peptides can facilitate their discovery and mechanistic understanding. In this study, we presented iMFP-LG, a method for multi-functional peptide identification based on protein language models (pLMs) and graph attention networks (GATs). Our comparative analyses demonstrated that iMFP-LG outperformed the state-of-the-art methods in identifying both multi-functional bioactive peptides and multi-functional therapeutic peptides. 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 peptides with both anti-microbial and anti-cancer functions from millions of known peptides in the UniRef90 database. As a result, eight candidate peptides were identified, among which one candidate was validated to process both anti-bacterial and anti-cancer properties 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.