DTBAffinity: A Multi-Modal Feature Engineering and Gradient-Boosting Framework for Drug–Target Binding Affinity on Davis and KIBA Benchmarks

An accurate prediction of how strongly a drug binds to its target (where the drug will have the desired effect) is very important for drug discovery. It helps select the most promising compounds and saves money by doing fewer experiments. We present DTBAffinity, a multi-modal regression framework that integrates chemically meaningful ligand descriptors with diverse protein sequence features in a unified gradient-boosting model. The representation of ligands includes physicochemical and topological descriptors (RDKit and Mordred), structural keys (MACCS and FP4), circular fingerprints (ECFP/Morgan), and SMILES-derived features from iFeatureOmega. For proteins, thousands of sequence-derived descriptors (composition, autocorrelations, physicochemical profiles, and evolutionary indices) from iFeatureOmega are used, together with contextual embeddings from large protein language models (ESM-1b, ESM-2). The feature matrices are cleaned up, variance filtered, z-score scaled, and univariate selected before being concatenated and modeled with regularized XGBoost ensembles. We evaluate DTBAffinity on two kinase-centric datasets that are commonly used: Davis (30,056 interactions: pKd values) and KIBA (118,254 interactions: integrated affinity scores). Various metrics are used to measure the performance, such as MSE, R2, Pearson/Spearman correlations, Concordance Index (CI), rm2, and AUPR. On Davis, DTBAffinity yields MSE = 0.1885, CI = 0.9102, and AUPR = 0.8112, and on KIBA, it gives MSE = 0.1540, CI = 0.8686, and AUPR = 0.8361; thus, it is better than the state-of-the-art baselines such as KronRLS, SimBoost, DeepDTA, and GraphDTA. The findings here imply that the combination of interpretable descriptors and contextual embeddings in a robust boosting framework is a great way to realize accurate, interpretable, and generalizable DTBA prediction.