Abstract Reverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. An adiabatic quantum computer (AQC) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The AQC is found to be competitive in identifying optimal solutions and future generations of AQCs may be able to outperform classical GAs. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.
Abstract Reverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. An adiabatic quantum computer (AQC) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The AQC is found to be competitive in identifying optimal solutions and future generations of AQCs may be able to outperform classical GAs. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.
Reverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. A Quantum Annealer (QA) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The QA is found to be competitive in identifying optimal solutions. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.
Optimizing the mRNA codon has an essential impact on gene expression for a specific target protein. It is an NP-hard problem; thus, exact solutions to such optimization problems become computationally intractable for realistic problem sizes on both classical and quantum computers. However, approximate solutions via heuristics can substantially impact the application they enable. Quantum approximate optimization is an alternative computation paradigm promising for tackling such problems. Recently, there has been some research in quantum algorithms for bioinformatics, specifically for mRNA codon optimization. This research presents a denser way to encode codons for implementing mRNA codon optimization via the variational quantum eigensolver algorithms on a gate-based quantum computer. This reduces the qubit requirement by half compared to the existing quantum approach, thus allowing longer sequences to be executed on existing quantum processors. The performance of the proposed algorithm is evaluated by comparing its results to exact solutions, showing well-matching results.
Codon optimization is a challenging combinatorial optimization problem with important applications in synthetic biology, protein expression, and biotechnology. While quantum annealing has previously been explored for this problem, the application of gate-based quantum algorithms remains largely unexplored. In this work, we present a gate-based quantum computing framework for codon optimization by formulating the optimization objective as an Ising Hamiltonian and expressing it in terms of Pauli operators suitable for gate-based quantum processors. The proposed framework is investigated using the Variational Quantum Eigensolver (VQE), Sampling Variational Quantum Eigensolver (SVQE), and the Quantum Approximate Optimization Algorithm (QAOA), with benchmarking against exact diagonalization, classical optimization, and quantum annealing. Using a three-amino-acid benchmark, the proposed implementations successfully reproduce the exact ground-state solutions while identifying optimized ansatz selections, optimization strategies, initialization schemes, and hardware execution settings that provide reproducible performance on current noisy quantum hardware. Hardware demonstrations are performed on IBM Quantum processors to evaluate the practical implementation of the proposed workflow. As a work in progress, this study establishes a reproducible computational framework for gate-based quantum codon optimization and provides the foundation for future investigations of larger protein sequences as quantum hardware and algorithms continue to advance.
Co-optimizing mRNA sequences for both codon optimality and secondary structure is crucial for producing stable and efficacious mRNA therapeutics. Codon optimization, which adjusts nucleotide sequences to enhance translational efficiency, inherently influences mRNA secondary structure - a key determinant of molecular stability both in-vial and in-cell. Because both properties are governed by the same underlying sequence, optimizing one directly impacts the other. To address this interdependence, we introduce a novel variational framework that simultaneously optimizes codon usage and secondary structure. Our method employs a dual-objective function that balances the codon adaptation index (CAI) and minimum free energy (MFE), incorporating variational parameters for codon selection. Leveraging a hybrid quantum-classical computational strategy and building on prior advancements in quantum algorithms for secondary structure prediction, we effectively navigate this complex optimization space. We demonstrate the feasibility of executing this end-to-end workflow on real quantum hardware, using IBM's 127-qubit Eagle processor. We validate our approach through both simulations and quantum hardware experiments on sequences of up to 30 nucleotides. These results highlight the potential of our framework to accelerate the design of optimal mRNA constructs for therapeutic and research applications.
A study published on bioRxiv proposes for the first time a hybrid approach combining quantum annealing and the Lagrange multiplier method by formulating the codon optimization problem as a constrained quadratic binary problem. It demonstrates the overwhelming performance of this quantum-classical hybrid protocol by applying it to practical scenarios: optimizing the SARS-CoV-2 spike protein sequence in a human host and the insulin sequence in an E. coli host. As a result of evaluating biological metrics, it established a robust workflow through which quantum computing can practically contribute to next-generation genetic engineering and new drug development by successfully optimizing codon usage patterns that govern protein translation efficiency and stability. [Quantum Biology Society] To efficiently produce specific proteins in heterologous hosts, a codon optimization process that adjusts the genetic code and codon usage frequencies to suit the host's characteristics is essential. While this is a core task in biotechnology to maximize the expression level and stability of therapeutic proteins like vaccines or insulin, the exponentially large number of possible gene sequence combinations has incurred massive computational costs to find optimal solutions using conventional classical computing methods. Recently, the achievements of a domestic research team that achieved groundbreaking optimization by directly applying quantum computing to this complex biological problem have been published. The paper titled "Quantum-classical hybrid approach for codon optimization and its practical applications," published on the preprint repository bioRxiv, presents a new protocol that will change the paradigm of gene sequence design utilizing quantum annealing. A joint domestic research team led by Professor Joonsuk Huh and researcher You Kyoung Chung from the Department of Chemistry at Sungkyunkwan University, Professor Daniel K Park from the Department of Applied Statistics at Yonsei University, and researcher Dongkeun Lee from the Korea Institute of Science and Technology Information (KISTI) spearheaded this innovative research. ■ Transformation into a Constrained Quadratic Binary Problem and Quantum Computation The research team newly formulated the complex codon optimization process into a mathematical constrained quadratic binary problem. In particular, they adopted a quantum-classical hybrid approach that organically integrates the parallel computing capabilities of quantum annealing hardware with the Lagrange multiplier method, a classical numerical analysis technique. Through this, they overcame the computational bottleneck occurring in the vast sequence search space and rapidly and accurately derived the optimal gene sequence that can maximize protein translation efficiency while simultaneously considering the host's codon usage bias. ■ Demonstrated Achievements Applied to COVID-19 Vaccine and Insulin The true value of this hybrid protocol was clearly proven through two practical biological scenarios. The research team successfully applied this algorithm to models for optimizing the codon sequence of the SARS-CoV-2 spike protein tailored to a human host environment and optimizing the insulin sequence within an E. coli host. As a result of rigorous biological metric evaluations, the sequences designed by the quantum algorithm demonstrated an overwhelming ability to perfectly optimize the codon usage patterns that govern protein translation efficiency. This demonstration is an important milestone declaring that quantum computing technology has moved beyond mere theoretical possibility to establish itself as a powerful and practical tool that can immediately contribute to next-generation gene therapeutics and customized new drug design pipelines. https://www.biorxiv.org/content/10.1101/2024.06.08.598046v1
Using quantum computing for drug design is among the most promising applications in quantum technologies. Genetic algorithms with their evolutionary iterations make it a propitious approach in various tasks, including drug discovery, gene prediction, docking of ligands to receptors, and the design to combinatorial libraries. As its computational power and methods limits classical computing, quantum computing intends to break these limits with exponential computing capabilities. This application complements both quantum theory and genetic programming as we use true randomness with mutation and fitness function based on information encoded onto qubits storing quantum data. In this article, we present the results of encoding quantum data to our quantum genetic algorithm, which predicts the best possible drug structure to bind onto the target protein. The qubits hold the genome structure to perform bit string mutation over quantum gates. These results are later than compared to classical computing with various approaches in the evolutionary algorithm's parameters.