A Comprehensive Machine Learning Model for Metal-Ligand Binding Prediction: Applications in Chemistry and Biology

A machine-learning (ML) model that predicts metal-ligand binding constants was developed using the open-source Chemprop software. The model was trained on over 30,000 experimental log K₁ values, which include both protonation and metal-ligand stability constants, comprising over 3500 ligands and 10² metal ions from 73 total elements, thus generalizing beyond existing limited approaches, which focus only on specific metals or ligand families. The best-performing model included a combination of SMILES-based molecular representations along with descriptors for the metal ion and experimental conditions. It had an external test R² value of 0.942, and MAE value of 0.834. A "SMILES-only" simpler version also produced accurate predictions and preserved the binding trends, serving as a quick and easily accessible alternative for users without computational expertise. The SMILES-only model performed comparably to density functional theory (DFT) calculations but utilized a fraction of the computational resources. The model was successfully applied across diverse domains, including bioinorganic chemistry, heavy metal remediation, and sensor development and demonstrated its effectiveness as a rapid and reliable screening tool for both academic and industrial uses.