A Physically-Informed Subgraph Isomorphism Approach to Molecular Docking Using Quantum Annealers

TL;DR

This paper enhances quantum annealer-based molecular docking by incorporating physicochemical interactions into the QUBO formulation, improving docking accuracy over purely geometric approaches.

Contribution

It introduces a novel QUBO formulation that includes Coulomb, van der Waals, H-bond, and hydrophobic interactions for more accurate quantum annealing-based docking.

Findings

Inclusion of physical interactions improves docking accuracy.

Experimental results demonstrate the impact of physical terms on results.

The approach extends previous geometric-only models with physicochemical data.

Abstract

Molecular docking is a crucial step in the development of new drugs as it guides the positioning of a small molecule (ligand) within the pocket of a target protein. In the literature, a feasibility study explored the potential of D-Wave quantum annealers for purely geometric molecular docking, neglecting physicochemical interactions between the protein and the ligand and focusing solely on their simplified geometries. To achieve this, the ligands were represented as graphs incorporating their geometric properties and then mapped onto a grid that discretized the three-dimensional space of the protein pocket. The quality of the ligand pose on the protein pocket was evaluated through the isomorphism between the ligand graph and the spatial grid. This paper builds on the previous study by introducing physicochemical interactions between the protein-ligand pair into the QUBO problem to improve the accuracy of the docking results. This paper presents a novel QUBO formulation that includes Coulomb and van der Waals forces, together with components representing H-bond and hydrophobic interactions. We integrate these physical interactions as corrective terms to the previous purely geometric QUBO formulation, and provide experimental results using the D-Wave quantum annealers to demonstrate their impact on the accuracy of the docking results.