Efficient Quantum Protein Structure Prediction with Problem-Agnostic Ansatzes

Abstract

Accurately predicting protein structures from amino acid sequences remains a fundamental challenge in computational biology, with profound implications for understanding biological functions and enabling structure-based drug discovery. Quantum computing approaches based on coarse-grained lattice models combined with variational algorithms have been proposed as an initial step towards predicting protein structures using quantum computers. In this work, we introduce a more efficient quantum protein structure prediction workflow that bypasses the need for explicit Hamiltonian construction by employing a problem-agnostic ansatz. The ansatz is trained to minimize an energy-based cost function that can be efficiently computed on classical computers, eliminating the need for ancillary qubits and reducing circuit depth compared to previous Hamiltonian-based methods. This enables a more scalable approach for larger proteins and facilitates the inclusion of higher-order interactions, previously hard to achieve in quantum approaches. We validate our method by benchmarking a hardware-efficient ansatz on a large set of proteins with up to 26 amino acids, modeled on the tetrahedral, body-centered cubic, and face-centered cubic lattices, incorporating up to second-nearest-neighbor interactions. We assess the performance on both a noise-free simulator and the ibm_kingston quantum computer using a set of distinct metrics to probe different aspects of the prediction quality. These experiments push the boundaries of quantum methods for protein structure prediction, targeting sequences that are longer than those typically addressed in prior studies. Overall, the results highlight the scalability and versatility of our approach, while also identifying key areas for improvement to inform future algorithm development and hardware advancements.