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

一种用于金属-配体结合预测的综合机器学习模型:在化学和生物学中的应用

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Abstract

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 K(1) values, which include both protonation and metal-ligand stability constants, comprising over 3500 ligands and 10(2) 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 R(2) 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.

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