Molecular Docking is an important step in the drug discovery process that aims at calculating the location and 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 phase, the 3D representation of the molecule is manipulated according to its degrees of freedom: rigid roto-translation and fragment rotations along the rotating bonds. 

All this simulation requires vast computational resources to perform all the algorithms. The significant development of Quantum Computing (QC) in recent years offers an exponential enhancement of the computational power of quantum machines compared to traditional computers. This boost in performance will enable quantum computers to perform molecular docking.

In this project, Exscalate is focusing on one specific phase of the molecular docking procedure called Small Molecule Unfolding (SMU). This phase is used for removing the initial bias of the molecule, typically due to the 3D construction, by expanding the ligand to an unfolded shape. 

Exscalate is developing a problem-solving approach to SMU by selecting the ideal location of the ligand inside a protein pocket through Quantum Annealing (QA) techniques. By formulating the optimization problem as a Higher-order Unconstrained Binary Optimization (HUBO), it was then transformed it to Quadratic Unconstrained Binary Optimization (QUBO) in order to make it solvable by quantum solvers on the latest D-Wave hardware (D-Wave 2000Q, Advantage). 

The SMU problem has been defined considering the position of the rotatable bonds of the molecule as the optimization variables. Exscalate 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. 

Through this work Exscalate will understand the peculiarities and limitations of these computing devices and compare their performance with state-of-the-art molecular docking methods.

Being involved in technology projects such as this is an opportunity for Exscalate to contribute to a European effort focused on technological advancement and welfare. Supporting EU research such as this will help address the highest unmet medical needs such as pandemics and rare diseases. 

Link:https://www.quantumcomputinglab.cineca.it/en/2021/08/25/quantum-molecule-unfolding-2