AGL-Score: Algebraic Graph Learning Score for Protein–Ligand Binding Scoring, Ranking, Docking, and Screening

Although algebraic graph theory-based models have been widely applied in physical modeling and molecular studies, they are typically incompetent in the analysis and prediction of biomolecular properties, confirming the common belief that "one cannot hear the shape of a drum". A new development in the century-old question about the spectrum-geometry relationship is provided. Novel algebraic graph learning score (AGL-Score) models are proposed to encode high-dimensional physical and biological information into intrinsically low-dimensional representations. The proposed AGL-Score models employ multiscale weighted colored subgraphs to describe crucial molecular and biomolecular interactions in terms of graph invariants derived from graph Laplacian, its pseudo-inverse, and adjacency matrices. Additionally, AGL-Score models are integrated with an advanced machine learning algorithm to predict biomolecular macroscopic properties from the low-dimensional graph representation of biomolecular structures. The proposed AGL-Score models are extensively validated for their scoring power, ranking power, docking power, and screening power via a number of benchmark datasets, namely CASF-2007, CASF-2013, and CASF-2016. Numerical results indicate that the proposed AGL-Score models are able to outperform other state-of-the-art scoring functions in protein-ligand binding scoring, ranking, docking, and screening. This study indicates that machine learning methods are powerful tools for molecular docking and virtual screening. It also indicates that spectral geometry or spectral graph theory has the ability to infer geometric properties.