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

Fuente: arXiv
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Autori principali: Agathangelou, Anastasia, Manawadu, Dilhan, Tavernelli, Ivano
Natura: Preprint
Pubblicazione: 2025
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author Agathangelou, Anastasia
Manawadu, Dilhan
Tavernelli, Ivano
author_facet Agathangelou, Anastasia
Manawadu, Dilhan
Tavernelli, Ivano
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2507_19383
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Quantum Algorithm for Protein Side-Chain Optimisation: Comparing Quantum to Classical Methods
Agathangelou, Anastasia
Manawadu, Dilhan
Tavernelli, Ivano
Quantum Physics
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.
title Quantum Algorithm for Protein Side-Chain Optimisation: Comparing Quantum to Classical Methods
topic Quantum Physics
url https://arxiv.org/abs/2507.19383