ABSTRACT Progress in quantum computation offers new opportunities for addressing longstanding combinatorial challenges. One such challenge is the Eternity II edge-matching puzzle, consisting of 256 tiles, which has resisted solution despite extensive community effort. The computational complexity of this NP-complete problem exceeds the capacity of current quantum annealing processors but lies within reach of hybrid quantum-classical solvers. Testing a quadratic unconstrained binary optimization (QUBO) model of a puzzle on a D-Wave hybrid solver demonstrates a complete solution only for puzzle instances up to 64 tiles. Simulated quantum annealing fails on this benchmark, whereas an original classical heuristic, “nucleation with deduction”, succeeds. To approach the full Eternity II puzzle, I developed a MATLAB package that integrates multiple quantum and classical approaches, including neural-network transformers and gradient-based refinement. A multistage computation pipeline is demonstrated successfully on a puzzle comparable in complexity to Eternity II and with a known solution, based on multiple hybrid optimization steps with both “hard” and “soft” constraint formulations, identification of persistent substructures, and a final classical refinement stage. The resulting optimization problem involves ∼100,000 logical variables and requires partial initialization. Intriguingly, solving this puzzle mirrors the “end game” of protein folding, a process that nature completes in mere fractions of a second, seemingly defying expectations set by the Levinthal paradox. The prospect of predicting protein structure by quantum annealing is reviewed in light of these results.
ABSTRACT Progress in quantum computation offers new opportunities for addressing longstanding combinatorial challenges. One such challenge is the Eternity II edge-matching puzzle, consisting of 256 tiles, which has resisted solution despite extensive community effort. The computational complexity of this NP-complete problem exceeds the capacity of current quantum annealing processors but lies within reach of hybrid quantum-classical solvers. Testing a quadratic unconstrained binary optimization (QUBO) model of a puzzle on a D-Wave hybrid solver demonstrates a complete solution only for puzzle instances up to 64 tiles. Simulated quantum annealing fails on this benchmark, whereas an original classical heuristic, “nucleation with deduction”, succeeds. To approach the full Eternity II puzzle, I developed a MATLAB package that integrates multiple quantum and classical approaches, including neural-network transformers and gradient-based refinement. A multistage computation pipeline is demonstrated successfully on a puzzle comparable in complexity to Eternity II and with a known solution, based on multiple hybrid optimization steps with both “hard” and “soft” constraint formulations, identification of persistent substructures, and a final classical refinement stage. The resulting optimization problem involves ∼100,000 logical variables and requires partial initialization. Intriguingly, solving this puzzle mirrors the “end game” of protein folding, a process that nature completes in mere fractions of a second, seemingly defying expectations set by the Levinthal paradox. The prospect of predicting protein structure by quantum annealing is reviewed in light of these results.
Quantum computing has progressed from a theoretical concept to a practical experimental technology. By processing information according to quantum mechanics rather than classical rules, quantum computers may offer advantages for certain problems. Although a few algorithms have proven speedups, it remains unclear where quantum computers will be practically useful, especially since current devices are noisy, small, and not yet fault tolerant. This thesis explores quantum computing for biophysically motivated combinatorial problems, with a focus on lattice protein models. In these simplified models, a protein is represented as a chain on a discrete lattice. Despite their simplicity, lattice proteins retain important features of real proteins, such as such as the folding of a chain with exponentially many possible shapes to a unique minimum-energy structure and steric constraints.To run lattice protein problems on quantum hardware, they must first be formulated using binary variables and objective functions. The latter typically contain soft constraints needed to ensure physical solutions. In Papers~\I--\II, we developed and extended a coordinate-based mapping for lattice protein folding, enabling D-Wave's hybrid quantum-classical annealer to fold both 2D hydrophobic-polar and 3D Miyazawa-Jernigan lattice proteins. In Paper~\III, we adapted the approach to the gate-based paradigm and showed how quadratic soft constraints could be removed by a mixer developed for the maximum-independent-set problem. Papers~\IV--\V addressed lattice protein design using quantum annealing, quantum approximate optimization algorithm, quantum alternating operator ansatz and hardware-efficient ansatz, while Paper~\VI extended the framework to multi-chain thermodynamics and the reconstruction of densities of states and heat-capacity features.Together, these papers show how folding, design, and multi-chain thermodynamics can be formulated, implemented, and analyzed using present-day quantum and hybrid hardware. A recurring limitation is the treatment of soft constraints. In quantum annealing, their high connectivity leads to error accumulation. On gate-based hardware, they increase circuit depth and sensitivity to noise. At the same time, temporary constraint violations can provide useful freedom during optimization. Further progress will therefore require improved formulations, algorithms and hardware that reduce the cost of enforcing physical solutions while retaining this flexibility.
Quantum annealing offers a promising paradigm for solving NP-hard combinatorial optimization problems, but its practical application is severely hindered by two challenges: the complex, manual process of translating problem descriptions into the requisite Quadratic Unconstrained Binary Optimization (QUBO) format and the scalability limitations of current quantum hardware. To address these obstacles, we propose a novel end-to-end framework, LLM-QUBO, that automates this entire formulation-to-solution pipeline. Our system leverages a Large Language Model (LLM) to parse natural language, automatically generating a structured mathematical representation. To overcome hardware limitations, we integrate a hybrid quantum-classical Benders' decomposition method. This approach partitions the problem, compiling the combinatorial complex master problem into a compact QUBO format, while delegating linearly structured sub-problems to classical solvers. The correctness of the generated QUBO and the scalability of the hybrid approach are validated using classical solvers, establishing a robust performance baseline and demonstrating the framework's readiness for quantum hardware. Our primary contribution is a synergistic computing paradigm that bridges classical AI and quantum computing, addressing key challenges in the practical application of optimization problem. This automated workflow significantly reduces the barrier to entry, providing a viable pathway to transform quantum devices into accessible accelerators for large-scale, real-world optimization challenges.
Quantum annealing has shown promise for finding solutions to difficult optimization problems, including protein folding. Recently, we used the D-Wave Advantage quantum annealer to explore the folding problem in a coarse-grained lattice model, the HP model, in which amino acids are classified into two broad groups: hydrophobic (H) and polar (P). Using a set of 22 HP sequences with up to 64 amino acids, we demonstrated the fast and consistent identification of the correct HP model ground states using the D-Wave hybrid quantum-classical solver. An equally relevant biophysical challenge, called the protein design problem, is the inverse of the above, where the task is to predict protein sequences that fold to a given structure. Here, we approach the design problem by a two-step procedure implemented and executed on a D-Wave machine. In the first step, we perform a pure sequence-space search by varying the type of amino acid at each sequence position, and seek sequences which minimize the HP-model energy of the target structure. After mapping this task onto an Ising spin-glass representation, we employ a hybrid quantum-classical solver to deliver energy-optimal sequences for structures with 30–64 amino acids, with a 100% success rate. In the second step, we filter the optimized sequences from the first step according to their ability to fold to the intended structure. In addition, we try solving the sequence optimization problem using only the quantum processing unit (QPU), which confines us to sizes ≤20 , due to exponentially decreasing success rates. To shed light on the pure QPU results, we investigate the effects of control errors caused by an imperfect implementation of the intended Hamiltonian on the QPU, by numerically analyzing the Schrödinger equation. We find that the simulated success rates in the presence of control noise semiquantitatively reproduce the modest pure QPU results for larger chains. Published by the American Physical Society 2024
Quantum optimization shows significant potential in tackling complex combinatorial challenges, prompting our research exploration into the domain of quantum computing to address the Bin Packing Problem (BPP) through Quadratic Unconstrained Binary Optimization (QUBO) formulations. This work-in-progress paper outlines our proposal for a thorough study that encompasses classical bin packing formulations, initiating with the Mixed Integer Linear Program, followed by a comparative analysis of the corresponding QUBO representations, and adopting a structured approach of Quantum Annealing on the D-Wave machine. While our work is still in progress, continuous comparative analyses are being conducted to evaluate various QUBO formulations, derived from diverse classical bin packing models, aiming to identify the most efficient QUBO for addressing the BPP. On another front, efforts are dedicated to refining the solution process further, with a focus on enhancing the precision of the selected QUBO formulation.
Steric clashes pose a challenge when exploring dense protein systems using conventional explicit-chain methods. A minimal example is a single lattice protein confined on a minimal grid, with no free sites. Finding its minimum energy is a hard optimization problem, with similarities to scheduling problems. It can be recast as a quadratic unconstrained binary optimization (QUBO) problem amenable to classical and quantum approaches. We show that this problem in its QUBO form can be swiftly and consistently solved for chain length 48, using either classical simulated annealing or hybrid quantum-classical annealing on a D-Wave system. In fact, the latter computations required about 10 s. We also test linear and quadratic programming methods, which work well for a lattice gas but struggle with chain constraints. All methods are benchmarked against exact results obtained from exhaustive structure enumeration, at a high computational cost.
Quantum error-correcting codes (QECCs) are at the heart of fault-tolerant quantum computing. As the size of quantum platforms is expected to grow, one of the open questions is to design new optimal codes of ever-increasing size. A related challenge is to certify the quality of a given code by evaluating its minimum distance, a quantity characterizing code's capacity to preserve quantum information. This problem is known to be NP-hard. Here we propose to harness the power of contemporary quantum platforms to address this question, and in this way help design quantum platforms of the future. Namely, we introduce an approach to compute the minimum distance of quantum stabilizer codes by reformulating the problem as a Quadratic Unconstrained Binary Optimization (QUBO) problem and leveraging established QUBO algorithms and heuristics as well as quantum annealing (QA) to address the latter. The reformulation as a QUBO introduces only a logarithmic multiplicative overhead in the required number of variables. We demonstrate the formulation using the D-Wave Advantage 4.1 quantum annealer and the hybrid quantum-classical algorithm Qbsolv, and benchmark the resulting QUBO-based implementations against specialized classical distance-finding methods. The QA- and SA-assisted implementations show broadly comparable performance, while the classical comparison clarifies the relative strengths of heuristic optimization and exact distance certification. Our results establish a solver-independent QUBO formulation with only a logarithmic multiplicative overhead in the number of variables and characterize connectivity and minor embedding as central limitations of its present implementation on quantum-annealing hardware.