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arXiv:2609.05238

Quantum Optimisation for Protein-Protein Interaction Network Alignment

Merle Stahl, Robert J. Banks, Matthias Traube, Josua Unger, Wolfgang Lechner, Jan Baumbach, Mhaned Oubounyt

quant-phq-bio.MNSubmitted Sep 4, 2026• Announced Sep 7, 2026• 0 citations
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Abstract

Protein-protein interaction (PPI) network alignment combines topological and sequence information to identify conserved modules across species, but global alignment remains challenging: heuristics sacrifice optimality, while exact methods lack scalability. We model the alignment as a weighted maximum common induced subgraph problem and reformulate it through the modular product graph to a minimum-weight vertex cover on the complement, with node weights carrying sequence similarity. To solve this problem, we develop a hybrid framework combining kernelisation, branch-and-bound, and seven Quantum Approximate Optimisation Algorithm (QAOA) formulations. These formulations differ in how the cover constraints are enforced, from penalty terms in the cost Hamiltonian to mixers confined to the feasible subspace. For single round QAOA, we derive closed-form expressions for the expected cost of four circulant mixer variants, enabling performance characterisation without circuit simulation. Applied to synthetic and real-world networks reduced to KEGG pathways, the QAOA formulations achieve high topological conservation on the aligned core while at least maintaining biological conservation comparable to leading classical aligners, at the cost of reduced node coverage. Across selected KEGG pathways, the aligned subnetworks retain disease-associated proteins, preserving biologically relevant information. Cheaper formulations leave more edges uncovered, while enforcing feasibility in the mixer raises circuit depth by one to two orders of magnitude. Together, these results highlight the potential of quantum optimisation for PPI network alignment and the resource trade-offs that will shape its scalability as quantum hardware matures.

Related papers

Penalty-free quantum optimization applied to lattice protein folding

Leif Gellersen, Anders Irbäck, Lucas Knuthson +1 more

Identifying minimum-energy structures of lattice proteins is a challenging discrete optimization problem. Quantum approaches such as analog quantum annealing and the gate-based quantum approximate optimization algorithm (QAOA) can address this problem after mapping it to a binary representation, which typically involves introducing penalty terms to enforce valid chain configurations. However, in this and many related problems, the use of quadratic penalty terms can be avoided by restricting the search space to independent sets in a conflict graph and using a QAOA mixer designed for the maximum independent set problem. In this work, we implement and explore this QAOA variant for lattice protein folding. Here, the objective function consists solely of the protein energy together with a simple linear bias term, without quadratic penalties. We validate this approach through classical simulations of the quantum circuits for lattice proteins of lengths $N=4$ and $N=6$. To explore larger systems, we further introduce a heuristic iterative local-search scheme, with which we successfully fold lattice proteins with lengths up to $N=14$ using local subgraphs with at most 26 qubits.

quant-pharXiv:2606.02104•Jun 2, 2026•0 citations

Solving Correlation Clustering with the Quantum Approximate Optimisation Algorithm

Jordi R. Weggemans

The quantum approximation optimisation algorithm (QAOA) is one of the leading candidates for testing the applicability of gate-model quantum resources at solving optimisation problems on small-sized quantum hardware. A combinatorial problem that has been understudied with QAOA is correlation clustering: given a weighted (+1,-1) graph, where the edge weights indicate whether two nodes are similar (positive edge weight) or different (negative edge weight), the task in correlation clustering is to find a clustering that either maximises agreements, minimises disagreements or a combination of both. In this thesis, we design Hamiltonian formulations that encode correlation clustering problems such that they can be solved with QAOA. For all Hamiltonian formulations we propose circuit implementations and study their complexities. To benchmark the performances of a basic QAOA algorithm using these formulations, we use numerical simulations on complete graph data sets. For one of the formulations, which uses a multi-level approach naturally suitable to qudit systems, we investigate the performances of several optimisers and introduce heuristic strategies to further improve its performance. On all instances in our data-sets, which include complete as well as Erdős–Renyi graphs, the improved algorithm shows competitive performances for QAOA depth p ≥ 2. We also show that for this algorithm at p = 1 parameters exists such that it has a performance guarantee of 0.670 on 3-regular graphs.

•Jan 1, 2020•1 citation

Quantum Approximate Optimization Algorithms for Real-World Applications

Erik Lindberg, Ivan Lindberg

The Quantum Approximate Optimisation Algorithm (QAOA) has emerged as a leading candidate for near-term quantum advantage in combinatorial optimisation, but most evaluations remain confined to synthetic benchmarks such as random MaxCut instances. Translating QAOA to real-world problem instances -- with irregular graph structures, heterogeneous constraint types, and practical scale requirements -- introduces additional challenges including QUBO formulation overhead, hardware embedding costs, and the performance gap between QAOA on structured real instances vs. random benchmarks. This paper presents the Real-World QAOA (RW-QAOA) framework, a systematic methodology for applying QAOA to four real-world application domains: supply chain network optimisation, financial portfolio rebalancing, telecommunications frequency assignment, and traffic signal timing optimisation. RW-QAOA introduces three methodological contributions: a domain-adaptive QUBO formulator (DAQF) encoding real-world constraints as penalised QUBO terms with penalty coefficient auto-tuning; a warm-start initialisation strategy (WSIS) using classical heuristic solutions to seed QAOA parameter search; and a layered noise adaptation protocol (LNAP) adjusting circuit depth based on real-time device calibration data. RW-QAOA is evaluated on real problem instances from industry partners across all four domains on IBM Quantum Eagle (127-qubit). RW-QAOA achieves solution quality within 4.2% of classical exact solvers across all four domains, outperforming classical greedy heuristics by 12.4% (SD = 3.8%) on average. WSIS reduces QAOA parameter convergence iterations by 48.4%. LNAP improves approximation ratio by 8.4pp vs. fixed-depth QAOA under device noise variation.

Quantum Frontiers Journal•Mar 28, 2024•0 citations

Exploring Network-Related Optimization Problems Using Quantum Heuristics

Zhihui Wang, Eleanor Gilbert Rieffel, Mustafa Adnane +4 more

Network-related connectivity optimization problems are underlying a wide range of applications and are also of high computational complexity. We consider studying network optimization problems using two types of quantum heuristics.One is quantum annealing, and the other Quantum Alternating Operator Ansatz, an extension of the Quantum Approximate Optimization Algorithms for gate-model quantum computation, in which a cost-function based unitary and a non-commuting mixing unitary are applied alternately. We present problem mappings for problems of finding the spanning-tree or spanning-graph of a graph that optimizes certain costs, and a variant that further requires the spanning-tree be degree-bounded. With quantum annealing, all constraints are cast into penalty terms in the cost Hamiltonian, and the solution is encoded as the ground state of the Hamiltonian. We provide three mappings to the quadratic unconstrained binary optimization (QUBO) form, compare the resource requirements, and analyze the tradeoffs. For QAOA, we give special focus on the design of mixers based on the constraints presented in the problem, such that the system evolution remains in a subspace of the full Hilbert space where all constraints are satisfied. In the spanning-tree problem, one such hard constraint is that a mixer applied to a spanning-tree needs also be a spanning tree. This involves checking the connectivity of a subgraph, which is a global condition common for most network-related problems. We show how this feature can be efficiently represented in the mixer in a quantum coherent way, based on manipulation of a descendant-matrix and an adjacent matrix. We further develop a mixer for the spanning-graphs based on the spanning-tree mixer.

•Jan 14, 2019•0 citations

Multiple Network Alignment on Quantum Computers

Anmer Daskin, Ananth Y. Grama, Sabre Kais

Comparative analyses of graph structured datasets underly diverse problems. Examples of these problems include identification of conserved functional components (biochemical interactions) across species, structural similarity of large biomolecules, and recurring patterns of interactions in social networks. A large class of such analyses methods quantify the topological similarity of nodes across networks. The resulting correspondence of nodes across networks, also called node alignment, can be used to identify invariant subgraphs across the input graphs. Given k graphs as input, alignment algorithms use topological information to assign a similarity score to each k-tuple of nodes, with elements (nodes) drawn from each of the input graphs. Nodes are considered similar if their neighbors are also similar. An alternate, equivalent view of these network alignment algorithms is to consider the Kronecker product of the input graphs, and to identify high-ranked nodes in the Kronecker product graph. Conventional methods such as PageRank and HITS (Hypertext Induced Topic Selection) can be used for this purpose. These methods typically require computation of the principal eigenvector of a suitably modified Kronecker product matrix of the input graphs. We adopt this alternate view of the problem to address the problem of multiple network alignment. Using the phase estimation algorithm, we show that the multiple network alignment problem can be efficiently solved on quantum computers. We characterize the accuracy and performance of our method, and show that it can deliver exponential speedups over conventional (non-quantum) methods. I.

•Aug 15, 2016•1 citation

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

Anastasia Agathangelou, Dilhan Manawadu, Ivano Tavernelli

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.

arXiv:2507.19383•Jul 25, 2025•0 citations
Protein-protein interaction (PPI) network alignment combines topological and sequence information to identify conserved modules across species, but global alignment remains challenging: heuristics sacrifice optimality, while exact methods lack scalability. We model the alignment as a weighted maximum common induced subgraph problem and reformulate it through the modular product graph to a minimum-weight vertex cover on the complement, with node weights carrying sequence similarity. To solve this problem, we develop a hybrid framework combining kernelisation, branch-and-bound, and seven Quantum Approximate Optimisation Algorithm (QAOA) formulations. These formulations differ in how the cover constraints are enforced, from penalty terms in the cost Hamiltonian to mixers confined to the feasible subspace. For single round QAOA, we derive closed-form expressions for the expected cost of four circulant mixer variants, enabling performance characterisation without circuit simulation. Applied to synthetic and real-world networks reduced to KEGG pathways, the QAOA formulations achieve high topological conservation on the aligned core while at least maintaining biological conservation comparable to leading classical aligners, at the cost of reduced node coverage. Across selected KEGG pathways, the aligned subnetworks retain disease-associated proteins, preserving biologically relevant information. Cheaper formulations leave more edges uncovered, while enforcing feasibility in the mixer raises circuit depth by one to two orders of magnitude. Together, these results highlight the potential of quantum optimisation for PPI network alignment and the resource trade-offs that will shape its scalability as quantum hardware matures.
Identifying minimum-energy structures of lattice proteins is a challenging discrete optimization problem. Quantum approaches such as analog quantum annealing and the gate-based quantum approximate optimization algorithm (QAOA) can address this problem after mapping it to a binary representation, which typically involves introducing penalty terms to enforce valid chain configurations. However, in this and many related problems, the use of quadratic penalty terms can be avoided by restricting the search space to independent sets in a conflict graph and using a QAOA mixer designed for the maximum independent set problem. In this work, we implement and explore this QAOA variant for lattice protein folding. Here, the objective function consists solely of the protein energy together with a simple linear bias term, without quadratic penalties. We validate this approach through classical simulations of the quantum circuits for lattice proteins of lengths N=4N=4N=4 and N=6N=6N=6. To explore larger systems, we further introduce a heuristic iterative local-search scheme, with which we successfully fold lattice proteins with lengths up to N=14N=14N=14 using local subgraphs with at most 26 qubits.
The quantum approximation optimisation algorithm (QAOA) is one of the leading candidates for testing the applicability of gate-model quantum resources at solving optimisation problems on small-sized quantum hardware. A combinatorial problem that has been understudied with QAOA is correlation clustering: given a weighted (+1,-1) graph, where the edge weights indicate whether two nodes are similar (positive edge weight) or different (negative edge weight), the task in correlation clustering is to find a clustering that either maximises agreements, minimises disagreements or a combination of both. In this thesis, we design Hamiltonian formulations that encode correlation clustering problems such that they can be solved with QAOA. For all Hamiltonian formulations we propose circuit implementations and study their complexities. To benchmark the performances of a basic QAOA algorithm using these formulations, we use numerical simulations on complete graph data sets. For one of the formulations, which uses a multi-level approach naturally suitable to qudit systems, we investigate the performances of several optimisers and introduce heuristic strategies to further improve its performance. On all instances in our data-sets, which include complete as well as Erdős–Renyi graphs, the improved algorithm shows competitive performances for QAOA depth p ≥ 2. We also show that for this algorithm at p = 1 parameters exists such that it has a performance guarantee of 0.670 on 3-regular graphs.
The Quantum Approximate Optimisation Algorithm (QAOA) has emerged as a leading candidate for near-term quantum advantage in combinatorial optimisation, but most evaluations remain confined to synthetic benchmarks such as random MaxCut instances. Translating QAOA to real-world problem instances -- with irregular graph structures, heterogeneous constraint types, and practical scale requirements -- introduces additional challenges including QUBO formulation overhead, hardware embedding costs, and the performance gap between QAOA on structured real instances vs. random benchmarks. This paper presents the Real-World QAOA (RW-QAOA) framework, a systematic methodology for applying QAOA to four real-world application domains: supply chain network optimisation, financial portfolio rebalancing, telecommunications frequency assignment, and traffic signal timing optimisation. RW-QAOA introduces three methodological contributions: a domain-adaptive QUBO formulator (DAQF) encoding real-world constraints as penalised QUBO terms with penalty coefficient auto-tuning; a warm-start initialisation strategy (WSIS) using classical heuristic solutions to seed QAOA parameter search; and a layered noise adaptation protocol (LNAP) adjusting circuit depth based on real-time device calibration data. RW-QAOA is evaluated on real problem instances from industry partners across all four domains on IBM Quantum Eagle (127-qubit). RW-QAOA achieves solution quality within 4.2% of classical exact solvers across all four domains, outperforming classical greedy heuristics by 12.4% (SD = 3.8%) on average. WSIS reduces QAOA parameter convergence iterations by 48.4%. LNAP improves approximation ratio by 8.4pp vs. fixed-depth QAOA under device noise variation.
Network-related connectivity optimization problems are underlying a wide range of applications and are also of high computational complexity. We consider studying network optimization problems using two types of quantum heuristics.One is quantum annealing, and the other Quantum Alternating Operator Ansatz, an extension of the Quantum Approximate Optimization Algorithms for gate-model quantum computation, in which a cost-function based unitary and a non-commuting mixing unitary are applied alternately. We present problem mappings for problems of finding the spanning-tree or spanning-graph of a graph that optimizes certain costs, and a variant that further requires the spanning-tree be degree-bounded. With quantum annealing, all constraints are cast into penalty terms in the cost Hamiltonian, and the solution is encoded as the ground state of the Hamiltonian. We provide three mappings to the quadratic unconstrained binary optimization (QUBO) form, compare the resource requirements, and analyze the tradeoffs. For QAOA, we give special focus on the design of mixers based on the constraints presented in the problem, such that the system evolution remains in a subspace of the full Hilbert space where all constraints are satisfied. In the spanning-tree problem, one such hard constraint is that a mixer applied to a spanning-tree needs also be a spanning tree. This involves checking the connectivity of a subgraph, which is a global condition common for most network-related problems. We show how this feature can be efficiently represented in the mixer in a quantum coherent way, based on manipulation of a descendant-matrix and an adjacent matrix. We further develop a mixer for the spanning-graphs based on the spanning-tree mixer.
Comparative analyses of graph structured datasets underly diverse problems. Examples of these problems include identification of conserved functional components (biochemical interactions) across species, structural similarity of large biomolecules, and recurring patterns of interactions in social networks. A large class of such analyses methods quantify the topological similarity of nodes across networks. The resulting correspondence of nodes across networks, also called node alignment, can be used to identify invariant subgraphs across the input graphs. Given k graphs as input, alignment algorithms use topological information to assign a similarity score to each k-tuple of nodes, with elements (nodes) drawn from each of the input graphs. Nodes are considered similar if their neighbors are also similar. An alternate, equivalent view of these network alignment algorithms is to consider the Kronecker product of the input graphs, and to identify high-ranked nodes in the Kronecker product graph. Conventional methods such as PageRank and HITS (Hypertext Induced Topic Selection) can be used for this purpose. These methods typically require computation of the principal eigenvector of a suitably modified Kronecker product matrix of the input graphs. We adopt this alternate view of the problem to address the problem of multiple network alignment. Using the phase estimation algorithm, we show that the multiple network alignment problem can be efficiently solved on quantum computers. We characterize the accuracy and performance of our method, and show that it can deliver exponential speedups over conventional (non-quantum) methods. I.
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.