GPCRact: a hierarchical framework for predicting ligand-induced GPCR activity via allosteric communication modeling.

ABSTRACT: Accurate prediction of ligand-induced activity for G-protein-coupled receptors (GPCRs) is a cornerstone of drug discovery, yet it is challenged by the need to model allosteric communication-the long-range signaling linking ligand binding to distal conformational changes. Prevailing sequence-based models often fail to capture these three-dimensional dynamics, a limitation frequently masked by averaged performance on simpler Class A targets. To address this, we introduce GPCRact, a novel framework that models the biophysical principles of allosteric modulation in GPCR activation. It first constructs a high-resolution, three-dimensional structure-aware graph from the heavy-atom coordinates of functionally critical residues at binding and allosteric sites. A dual attention architecture then ca

SUBMITTER: Son H 

PROVIDER: S-EPMC12805254 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature