Machine learning methods for pKa prediction of small molecules: Advances and challenges.

ABSTRACT

The acid-base dissociation constant (pKa) is a fundamental property influencing many ADMET properties of small molecules. However, rapid and accurate pKa prediction remains a great challenge. In this review, we outline the current advances in machine-learning-based QSAR models for pKa prediction, including descriptor-based and graph-based approaches, and summarize their pros and cons. Moreover, we highlight the current challenges and future directions regarding experimental data, crucial factors influencing pKa and in silico prediction tools. We hope that this review can provide a practical guidance for the follow-up studies.