A Quantum Framework for Protein Binding‐Site Structure Prediction on Utility‐Level Quantum Processors
Source abstract
Abstract
Abstract Accurate prediction of protein active‐site structures remains a central challenge in structural biology, especially for short and flexible peptide fragments where conventional and simulation‐based methods often fail. Here, we present a quantum computing framework designed for utility‐level quantum processors to address this problem. Starting from an amino acid sequence, we cast structure prediction as a ground‐state energy minimization task using the Variational Quantum Eigensolver (VQE). Amino acid connectivity is represented on a tetrahedral lattice, and steric, geometric, and chirality constraints are encoded into a problem‐specific Hamiltonian expressed as sparse Pauli operators. A two‐stage architecture separates energy estimation from measurement decoding, enabling noise mitigation under realistic device conditions. We evaluate the method on 23 real protein fragments from the PDBbind dataset and 7 fragments from therapeutically relevant proteins, executing all experiments on the IBM–Cleveland Clinic quantum processor. Structural predictions are benchmarked against AlphaFold3 (AF3) and classical simulation–based approaches using identical postprocessing and docking procedures. Our quantum framework outperforms both AF3 and classical baselines in Root‐Mean‐Square Deviation (RMSD) and docking efficacy, demonstrating a practical end‐to‐end pipeline for biologically relevant structure prediction on real quantum hardware and highlighting its engineering feasibility for near‐term quantum devices.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Quantum Computing Algorithms and Architecture · Quantum-Dot Cellular Automata · Photoreceptor and optogenetics research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Computer Science Kent State University Kent OH 44240 USA
Cleveland Clinic Genome Center Cleveland Clinic Research Cleveland Clinic Cleveland OH 44195 USA
Qradle Inc. Kent OH 44240 USA
Department of Electrical and Computer Engineering George Mason University Fairfax VA 22030 USA
Computational Structural Biology Section National Cancer Institute Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory Frederick MD 21701 USA
Department of Human Molecular Genetics and Biochemistry Sackler School of Medicine Tel Aviv University Tel Aviv 6997801 Israel
Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA
Center for Experimental Therapeutics Cleveland Clinic Research Cleveland Clinic Cleveland OH 44106 USA
Department of Genomic Sciences and Systems Biology Cleveland Clinic Research Cleveland Clinic Cleveland OH 44195 USA
Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland OH 44195 USA
Funding
National Institute on Aging · National Institute of Neurological Disorders and Stroke · Foundation for the National Institutes of Health · National Science Foundation · Alzheimer's Association · American Heart Association
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