AI-Integrated QSAR Modeling for Enhanced Drug Discovery: From Classical Approaches to Deep Learning and Structural Insight

Integrating artificial intelligence (AI) with the Quantitative Structure-Activity Relationship (QSAR) has transformed modern drug discovery by empowering faster, more accurate, and scalable identification of therapeutic compounds. This review outlines the evolution from classical QSAR methods, such as multiple linear regression and partial least squares, to advanced machine learning and deep learning approaches, including graph neural networks and SMILES-based transformers. Molecular docking and molecular dynamics simulations are presented as cooperative tools that boost the mechanistic consideration and structural insight into the ligand-target interactions. Discussions on using PROTACs and targeted protein degradation, ADMET prediction, and public databases and cloud-based platforms to democratize access to computational modeling are well presented with priority. Challenges related to authentication, interpretability, regulatory standards, and ethical concerns are examined, along with emerging patterns in AI-driven drug development. This review is a guideline for using computational models and databases in explainable, data-rich and profound drug discovery pipelines.