Domenico Bonanni

Emanuele Triuzzi, Riccardo Mengoni, Francesco Micucci et al.

Molecular docking is an essential step in the drug discovery process involving the detection of three-dimensional poses of a ligand inside the active site of the protein. In this paper, we address the Molecular Docking search phase by formulating the problem in QUBO terms, suitable for an annealing approach. We propose a problem formulation as a weighted subgraph isomorphism between the ligand graph and the grid of the target protein pocket. In particular, we applied a graph representation to the ligand embedding all the geometrical properties of the molecule including its flexibility, and we created a weighted spatial grid to the 3D space region inside the pocket. Results and performance obtained with quantum annealers are compared with classical simulated annealing solvers.

Francesco Micucci, Matteo Barbieri, Gabriella Bettonte et al.

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.