•연구자: 의생명시스템학부 조광휘
•발표일: 2025.01.29
•DOI: https://doi.org/10.1186/s13321-024-00945-7
•Rahul Brahma et al., Journal of Cheminformatics(Q1), Volume 17, Issue 12, 2025
•Abstract
G protein-coupled receptors (GPCRs) play vital roles in various physiological processes, making them attractive drug discovery targets. Meanwhile, deep learning techniques have revolutionized drug discovery by facilitating efficient tools for expediting the identification and optimization of ligands. However, existing models for the GPCRs often focus on single-target or a small subset of GPCRs or employ binary classification, constraining their applicability for high throughput virtual screening. To address these issues, we introduce AiGPro, a novel multitask model designed to predict small molecule agonists (EC50) and antagonists (IC50) across the 231 human GPCRs, making it a first-in-class solution for large-scale GPCR profiling.
Leveraging multi-scale context aggregation and bidirectional multi-head cross-attention mechanisms, our approach demonstrates that ensemble models may not be necessary for predicting complex GPCR states and small molecule interactions. Through extensive validation using stratified tenfold cross-validation, AiGPro achieves robust performance with Pearson’s correlation coefficient of 0.91, indicating broad generalizability. This breakthrough sets a new standard in the GPCR studies, outperforming previous studies. Moreover, our first-in-class multi-tasking model can predict agonist and antagonist activities across a wide range of GPCRs, offering a comprehensive perspective on ligand bioactivity within this diverse superfamily. To facilitate easy accessibility, we have deployed a web-based platform for model access at https://aicadd.ssu.ac.kr/AiGPro.