A Physically-Informed Subgraph Isomorphism Approach to Molecular Docking Using Quantum Annealers
2026-04-10 • Emerging Technologies
Emerging Technologies
AI summaryⓘ
The authors improved a method for placing small drug molecules into protein pockets using a quantum computer called a D-Wave annealer. Previously, the method only considered how the shapes of molecules fit together, ignoring chemical forces. In this paper, the authors added important physical forces like electric charges and bonds between molecules to make the positioning more accurate. They tested their approach on the quantum annealer and showed that including these forces helped improve the results.
Molecular dockingQuantum annealingD-WaveQUBOLigandProtein pocketCoulomb forcesvan der Waals forcesHydrogen bondingHydrophobic interactions
Authors
Francesco Micucci, Matteo Barbieri, Gabriella Bettonte, Domenico Bonanni, Anita Camillini, Anna Fava, Daniele Gregori, Andrea R. Beccari, Gianluca Palermo
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.