Sampling a Rare Protein Transition Using Quantum Annealing.

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.

Sampling rare conformational transitions with a quantum computer.

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.