2025/05/09 by Vaibhaw Kumar, Kumar, Vaibhaw, Dimitris Alevras +21 · 4 citations
Biochemistry, Genetics and Molecular Biology · Computer Science · #FOS: Physical sciences #Quantum Computing Algorithms and Architecture #Quantum Physics (quant-ph) #RNA Interference and Gene Delivery #RNA and protein synthesis mechanisms
paper · pdf · doi:10.48550/arxiv.2505.05782
openalex publication_date 2025/05/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Accurate prediction of mRNA secondary structure is critical for understanding gene expression, translation efficiency, and advancing mRNA-based therapeutics. However, the combinatorial complexity of possible foldings, especially in long sequences, poses significant computational challenges for classical algorithms. In this work, we propose a scalable, quantum-centric optimization framework that integrates quantum sampling with classical post-processing to tackle this problem. Building on a Quadratic Unconstrained Binary Optimization (QUBO) formulation of the mRNA folding task, we develop two complementary workflows: a Conditional Value at Risk (CVaR)-based variational quantum algorithm enhanced with gauge transformations and local search, and an Instantaneous Quantum Polynomial (IQP) circuit-based scheme where training is done classically and sampling is delegated to quantum hardware. We demonstrate the effectiveness of these approaches using IBM quantum processors, solving problem instances with up to 156 qubits and circuits containing up to 950 nonlocal gates, corresponding to mRNA sequences of up to 60 nucleotides. Additionally, we validate scalability of the CVaR algorithm on a tensor network simulator, reaching up to 354 qubits in noiseless settings. These results demonstrate the growing practical capabilities of hybrid quantum-classical methods for tackling large-scale biological optimization problems.