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Folding lattice proteins confined on minimal grids using a quantum-inspired encoding

Anders Irbäck1,*, Lucas Knuthson1, and Sandipan Mohanty2

  • 1Computational Science for Health and Environment (COSHE), Centre for Environmental and Climate Science, Lund University, 223 62 Lund, Sweden
  • 2Jülich Supercomputing Centre, Forschungszentrum Jülich, D-52425 Jülich, Germany

  • *Contact author: anders.irback@cec.lu.se
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Phys. Rev. E 112, 045302 – Published 1 October, 2025

DOI: https://doi.org/10.1103/8n7p-7lh2

Abstract

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.

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Phys. Rev. E 112, 045302– Published 1 October, 2025
  • Received 25 June 2025
  • Accepted 1 September 2025
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