AI-driven drug discovery using transformer-based molecular representation learning

Abstract

The vast majority of chemically plausible, drug-like molecules remain unexplored due to the combinatorial scale of chemical space and the limited throughput of experimental screening. This is complicated by the lack of data and the inability to extrapolate predictive models to chemotypes that are not represented well. We introduce a transformer-based molecular modeling framework for target-specific potency prediction, trained on curated BindingDB bioactivity data across Alzheimer‘s, diabetes, and cancer targets to deliver accurate pIC50 regression and binary activity classification. It uses curated bioactivity data from BindingDB to build target-specific datasets and uses a Byte Latent Transformer (BLT) that is trained directly on SMILES strings to predict changes in compound activity and potency based on quantitative structure–activity relationships. The transformer captures both syntactic and higher-level chemical features of SMILES representations and performs byte-level predictions using a latent model trained on the same molecular information. Potency predictions are executed inside an engine of chemically described molecular search engine, which executes stochasticity, SMILES-based amount mutations benefit by the envisaged activity, drug-like rules, and adaptive seeking heuristics to prevent local minima. Optimized candidate molecules and local optima are generated through guided SMILES mutations, preserving structural diversity around high-potency leads. The framework delivers highly accurate pIC50 regression (R2 0.95–0.98) and binary activity classification across Alzheimer's, diabetes, and cancer targets, enabling robust virtual screening and lead prioritization for diverse biological targets.