Dowker complex based machine learning (DCML) models for protein-ligand binding affinity prediction

Xiang Liu, Huitao Feng, Jie Wu, Kelin Xia

Abstract: Author summary With the ever-increasing accumulation of chemical and biomolecular data, data-driven artificial intelligence (AI) models will usher in an era of faster, cheaper and more-efficient drug design and drug discovery. However, unlike image, text, video, audio data, molecular data from chemistry and biology, have much complicated three-dimensional structures, as well as physical and chemical properties. Efficient molecular representations and descriptors are key to the success of machine learning models in drug design. Here, we propose Dowker complex based molecular representation and Riemann Zeta function based molecular featurization, for the first time. To characterize the complicated molecular structures and interactions at the atomic level, Dowker complexes are constructed. Based on them, intrinsic mathematical invariants are derived and used as molecular descriptors, which can be further combined with machine learning and deep learning models. Our model has achieved state-of-the-art results in protein-ligand binding affinity prediction, demonstrating its great potential for other drug design and discovery problems.