Topological fingerprints reveal protein-ligand binding mechanism

Abstract: Protein-ligand binding is a fundamental biological process that is paramount to many other biological processes, such as signal transduction, metabolic pathways, enzyme construction, cell secretion, gene expression, etc. Accurate prediction of protein-ligand binding affinities is vital to rational drug design and the understanding of protein-ligand binding and binding induced function. Existing binding affinity prediction methods are inundated with geometric detail and involve excessively high dimensions, which undermines their predictive power for massive binding data. Topology provides an ultimate level of abstraction and thus incurs too much reduction in geometric information. Persistent homology embeds geometric information into topological invariants and bridges the gap between complex geometry and abstract topology. However, it over simplifies biological information. This work introduces element specific persistent homology (ESPH) to retain crucial biological information during topological simplification. The combination of ESPH and machine learning gives rise to one of the most efficient and powerful tools for revealing protein-ligand binding mechanism and for predicting binding affinities.