Relatore: Kevin Mato (Politecnico di Milano)


Molecular Docking is an important step of the drug discovery process which aims at calculating the preferred position and shape of one molecule to a second when they are bound to each other.

During this part of the in-silico analysis, a 3D representation of the molecules are manipulated according to their degree of freedoms: rigid roto-translation, and fragment rotations along the rotatable bonds.

In our work, we focused one specific phase of the molecular docking procedure that is called “Small Molecule Unfolding”, SMU. This phases is used for removing the initial bias of the molecule, typically due to the 3D construction, by expanding the ligand to an unfolded shape. 

We proposed a quantum annealing approach to SMU, by formulating the optimization problem as a High-order Unconstrained Binary Optimization (HUBO), and then we transformed it to QUBO in order to study make the solution feasible on the latest D-Wave hardware (D-Wave 2000Q, Advantage). The problem has been defined considering the position of the rotatable bonds of the molecule as the optimization variables. We assumed discrete possible rotation angles. The objective of the SMU problem is to find the molecule configuration that maximizes the molecular area, or equivalently, that maximizes the internal distances of the atoms that compose the molecule.