Quantum Algorithm for Protein Side-Chain Optimisation: Comparing Quantum to Classical Methods

Abstract: Modelling and predicting protein configurations is crucial for advancing drug discovery, enabling the design of treatments for life-threatening diseases. A critical aspect of this challenge is rotamer optimisation - the determination of optimal side-chain conformations given a fixed protein backbone. This problem, involving the internal degrees of freedom of amino acid side-chains, significantly influences the protein's overall structure and function. In this work, we develop a resource-efficient optimisation algorithm to compute the ground state energy of protein structures, with a focus on side-chain configuration. We formulate the rotamer optimisation problem as a Quadratic Unconstrained Binary Optimisation problem and map it to an Ising model, enabling efficient quantum encoding. Building on this formulation, we propose a quantum algorithm based on the Quantum Approximate Optimisation Algorithm to explore the conformational space and identify low-energy configurations. To benchmark our approach, we conduct a classical study using custom-built libraries tailored for structural characterisation and energy optimisation. Our quantum method demonstrates a reduction in computational cost compared to classical simulated annealing techniques, offering a scalable and promising framework for protein structure optimisation in the quantum era.