Structural rearrangements play a central role in the organization and function of complex biomolecular systems. In principle, Molecular Dynamics (MD) simulations enable us to investigate these thermally activated processes with an atomic level of resolution. In practice, an exponentially large fraction of computational resources must be invested to simulate thermal fluctuations in metastable states. Path sampling methods focus the computational power on sampling the rare transitions between states. One of their outstanding limitations is to efficiently generate paths that visit significantly different regions of the conformational space. To overcome this issue, we introduce a new algorithm for MD simulations that integrates machine learning and quantum computing. First, using functional integral methods, we derive a rigorous low-resolution spatially coarse-grained representation of the system's dynamics, based on a small set of molecular configurations explored with machine learning. Then, we use a quantum annealer to sample the transition paths of this low-resolution theory. We provide a proof-of-concept application by simulating a benchmark conformational transition with all-atom resolution on the D-Wave quantum computer. By exploiting the unique features of quantum annealing, we generate uncorrelated trajectories at every iteration, thus addressing one of the challenges of path sampling. Once larger quantum machines will be available, the interplay between quantum and classical resources may emerge as a new paradigm of high-performance scientific computing. In this work, we provide a platform to implement this integrated scheme in the field of molecular simulations.
Structural rearrangements play a central role in the organization and function of complex biomolecular systems. In principle, Molecular Dynamics (MD) simulations enable us to investigate these thermally activated processes with an atomic level of resolution. In practice, an exponentially large fraction of computational resources must be invested to simulate thermal fluctuations in metastable states. Path sampling methods focus the computational power on sampling the rare transitions between states. One of their outstanding limitations is to efficiently generate paths that visit significantly different regions of the conformational space. To overcome this issue, we introduce a new algorithm for MD simulations that integrates machine learning and quantum computing. First, using functional integral methods, we derive a rigorous low-resolution spatially coarse-grained representation of the system's dynamics, based on a small set of molecular configurations explored with machine learning. Then, we use a quantum annealer to sample the transition paths of this low-resolution theory. We provide a proof-of-concept application by simulating a benchmark conformational transition with all-atom resolution on the D-Wave quantum computer. By exploiting the unique features of quantum annealing, we generate uncorrelated trajectories at every iteration, thus addressing one of the challenges of path sampling. Once larger quantum machines will be available, the interplay between quantum and classical resources may emerge as a new paradigm of high-performance scientific computing. In this work, we provide a platform to implement this integrated scheme in the field of molecular simulations.
Simulating spontaneous structural rearrangements in macromolecules with classical molecular dynamics is an outstanding challenge. Conventional supercomputers can access time intervals of up to tens of μs, while many key events occur on exponentially longer time scales. Path sampling techniques have the advantage of focusing the computational power on barrier-crossing trajectories, but generating uncorrelated transition paths that explore diverse conformational regions remains a problem. We employ a hybrid path-sampling paradigm that addresses this issue by generating trial transition paths using a quantum annealing (QA) machine. We first employ a classical computer to perform an uncharted exploration of the conformational space. The data set generated in this exploration is then postprocessed using a path integral-based method to yield a coarse-grained network representation of the reactive kinetics. By resorting to a quantum annealer, quantum superposition can be exploited to encode all of the transition pathways in the initial quantum state, thus potentially solving the path exploration problem. Furthermore, each QA cycle yields a completely uncorrelated trial trajectory. We previously validated this scheme on a prototypically simple transition, which could be extensively characterized on a desktop computer. Here, we scale up in complexity and perform an all-atom simulation of a protein conformational transition that occurs on the millisecond time scale, obtaining results that match those of the Anton special-purpose supercomputer. Despite limitations due to the available quantum annealers, our study highlights how realistic biomolecular simulations provide potentially impactful new ground for applying, testing, and advancing quantum technologies.
Quantum annealing is a computational paradigm in which optimisation problems are mapped onto the energy landscape of an interacting quantum system and explored through its dynamical evolution. By continuously transforming a simple initial Hamiltonian into one whose ground state encodes the solution, the system traverses a complex landscape via a combination of quantum fluctuations, tunnelling processes, and dissipative dynamics. Unlike gate-based quantum computing, quantum annealing is a specialised and near-term approach aimed primarily at discrete optimisation and sampling tasks. While it is not expected to provide polynomial-time solutions to NP-hard problems in the worst case, it offers a physically motivated heuristic for navigating rugged energy landscapes that arise across science and engineering. Modern quantum annealers realise programmable spin systems with thousands of qubits, placing them among the largest controllable quantum devices currently available. As a result, their significance extends beyond optimisation: they also function as experimental platforms for studying non-equilibrium many-body quantum dynamics in regimes that are difficult to access using classical simulation. In this review we present an accessible introduction to the principles of quantum annealing, describe the main hardware platforms and algorithmic techniques, and analyse how tunnelling, spectral gaps, and open-system effects shape computational performance. We survey applications ranging from optimisation and machine learning to quantum simulation and many-body physics, and discuss the central challenges in benchmarking, scaling, and control. These perspectives position quantum annealing as a distinctive framework at the interface of optimisation, stochastic sampling, and programmable quantum dynamics, with a role that is complementary to both classical algorithms and gate-based quantum computing.
Finding the global minimum of a potential energy surface is a fundamental challenge in materials science, with applications ranging from protein folding to cluster physics and, more broadly, to systems in which the number of (meta)stable configurations grows prohibitively large. In recent decades, quantum annealing (QA) has emerged as a promising global optimization strategy, exploiting quantum fluctuations in contrast to the thermal fluctuations that drive its classical counterpart. Here, we introduce a novel implementation of QA based on path-integral molecular dynamics, an efficient and well-established framework for sampling the quantum nuclear density without the need to manipulate many-body wavefunctions explicitly. While retaining the flexibility and simplicity of molecular dynamics simulations, this quantum-annealing protocol delivers strong performance across a wide range of atomic systems, simulated by either empirical force fields or machine-learning interatomic potentials. The method can be used either as a global optimizer of the potential-energy surface, or as a quantum-informed structure-search strategy in which nuclear quantum effects are included directly in the optimization workflow -- a feature particularly relevant for materials such as high-pressure hydrides.
Quantum annealing is a computational paradigm in which optimisation problems are encoded in the energy landscape of an interacting quantum system and explored through its dynamical evolution. By continuously transforming an initial Hamiltonian into one whose ground state represents the solution, the system navigates complex energy landscapes through a combination of quantum fluctuations, tunnelling processes, and dissipative dynamics. Quantum annealing is primarily designed for discrete optimisation and sampling tasks and provides a physically motivated heuristic for exploring rugged landscapes that arise across science and engineering. Modern quantum annealers realise programmable spin systems with thousands of qubits, making them among the largest controllable quantum devices currently available. Beyond optimisation, they also serve as experimental platforms for studying non-equilibrium many-body quantum dynamics in regimes that are challenging to access classically. In this review we introduce the principles of quantum annealing, describe the main hardware platforms and algorithmic techniques, and analyse the roles of tunnelling, spectral gaps, and open-system effects in determining performance. We survey applications ranging from optimisation and machine learning to quantum simulation and many-body physics, and discuss the central challenges of benchmarking, scaling, and control. These developments position quantum annealing at the interface of optimisation, stochastic sampling, and programmable quantum dynamics.
This paper explores the potential of quantum computing to revolutionize molecular dynamics (MD) simulations, addressing the significant computational bottleneck currently limiting their widespread adoption. We propose a novel quantum algorithm, specifically leveraging quantum annealing, to efficiently navigate the complex conformational landscape of molecules, leading to dramatically accelerated simulations. The core claim is that this algorithm offers a significant improvement in speed and accuracy compared to traditional MD methods, particularly for large molecule systems. We detail the design of the quantum algorithm, its potential advantages, and preliminary results demonstrating its efficacy in a simplified model.
The ability to perform ab initio molecular dynamics simulations using potential energies calculated on quantum computers would allow virtually exact dynamics for chemical and biochemical systems, with substantial impacts on the fields of catalysis and biophysics. However, noisy hardware, the costs of computing gradients, and the number of qubits required to simulate large systems present major challenges to realizing the potential of dynamical simulations using quantum hardware. Here, we demonstrate that some of these issues can be mitigated by recent advances in machine learning. By combining transfer learning with techniques for building machine-learned potential energy surfaces, we propose a new path forward for molecular dynamics simulations on quantum hardware. We use transfer learning to reduce the number of energy evaluations that use quantum hardware by first training models on larger, less accurate classical datasets and then refining them on smaller, more accurate quantum datasets. We demonstrate this approach by training machine learning models to predict a molecule's potential energy using Behler-Parrinello neural networks. When successfully trained, the model enables energy gradient predictions necessary for dynamics simulations that cannot be readily obtained directly from quantum hardware. To reduce the quantum resources needed, the model is initially trained with data derived from low-cost techniques, such as Density Functional Theory, and subsequently refined with a smaller dataset obtained from the optimization of the Unitary Coupled Cluster ansatz. We show that this approach significantly reduces the size of the quantum training dataset while capturing the high accuracies needed for quantum chemistry simulations.