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Main Authors: Evenseth, Linn, Galewski, Kamil, Jarnicki, Witold, Lafiosca, Piero, Patel, Vyom N., Rajchel-Mieldzioć, Grzegorz, Šimka, Martin, Szczepanik, Michał, Żak, Emil
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2604.10487
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author Evenseth, Linn
Galewski, Kamil
Jarnicki, Witold
Lafiosca, Piero
Patel, Vyom N.
Rajchel-Mieldzioć, Grzegorz
Šimka, Martin
Szczepanik, Michał
Żak, Emil
author_facet Evenseth, Linn
Galewski, Kamil
Jarnicki, Witold
Lafiosca, Piero
Patel, Vyom N.
Rajchel-Mieldzioć, Grzegorz
Šimka, Martin
Szczepanik, Michał
Żak, Emil
contents We present a computational platform for modeling chemical reactions in complex molecular environments, focused on ligand-protein binding in drug discovery. The platform implements our new quantum-in-quantum-in-classical (QM/QM/MM) multiscale embedding model that integrates molecular dynamics with a quantum-information-enhanced density matrix embedding theory and quantum chemistry solvers, including explicit solvent. Quantum-information metrics are utilized to generate entanglement-consistent orbitals, enabling a high-accuracy description of strongly correlated regions. The framework supports multiple computational backends, including multi-CPU, NVIDIA multi-GPU architectures, and quantum hardware (IQM, IonQ, IBM) integrated under CUDA-Q, and is designed for compatibility with future fault-tolerant quantum systems. The new platform's capabilities are demonstrated by modeling covalent docking of zanubrutinib to Bruton's tyrosine kinase via a Michael addition mechanism, computing the full reaction energy profiles and energy barriers at a reduced computational cost relative to existing methods. As a 2nd-generation anticancer agent, zanubrutinib serves as a proof of concept for covalent inhibitor discovery. Accurate first-principles reaction barrier estimations provided by our method can contribute to reducing false positive and negative rates in drug discovery pipelines. Scalability is validated through benchmarks on GPU clusters, cloud-based CPU infrastructures. We demonstrate integration with quantum devices (up to 20 qubits), alongside resource estimates for fault-tolerant quantum computing, indicating potential speedups of up to 20x. Beyond single reactions, the platform supports the construction of reaction networks in chemical metric space, facilitating ligand screening and systematic exploration of reactive pathways.
format Preprint
id arxiv_https___arxiv_org_abs_2604_10487
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle CovAngelo: A hybrid quantum-classical computing platform for accurate and scalable drug discovery
Evenseth, Linn
Galewski, Kamil
Jarnicki, Witold
Lafiosca, Piero
Patel, Vyom N.
Rajchel-Mieldzioć, Grzegorz
Šimka, Martin
Szczepanik, Michał
Żak, Emil
Chemical Physics
Computational Physics
Quantum Physics
We present a computational platform for modeling chemical reactions in complex molecular environments, focused on ligand-protein binding in drug discovery. The platform implements our new quantum-in-quantum-in-classical (QM/QM/MM) multiscale embedding model that integrates molecular dynamics with a quantum-information-enhanced density matrix embedding theory and quantum chemistry solvers, including explicit solvent. Quantum-information metrics are utilized to generate entanglement-consistent orbitals, enabling a high-accuracy description of strongly correlated regions. The framework supports multiple computational backends, including multi-CPU, NVIDIA multi-GPU architectures, and quantum hardware (IQM, IonQ, IBM) integrated under CUDA-Q, and is designed for compatibility with future fault-tolerant quantum systems. The new platform's capabilities are demonstrated by modeling covalent docking of zanubrutinib to Bruton's tyrosine kinase via a Michael addition mechanism, computing the full reaction energy profiles and energy barriers at a reduced computational cost relative to existing methods. As a 2nd-generation anticancer agent, zanubrutinib serves as a proof of concept for covalent inhibitor discovery. Accurate first-principles reaction barrier estimations provided by our method can contribute to reducing false positive and negative rates in drug discovery pipelines. Scalability is validated through benchmarks on GPU clusters, cloud-based CPU infrastructures. We demonstrate integration with quantum devices (up to 20 qubits), alongside resource estimates for fault-tolerant quantum computing, indicating potential speedups of up to 20x. Beyond single reactions, the platform supports the construction of reaction networks in chemical metric space, facilitating ligand screening and systematic exploration of reactive pathways.
title CovAngelo: A hybrid quantum-classical computing platform for accurate and scalable drug discovery
topic Chemical Physics
Computational Physics
Quantum Physics
url https://arxiv.org/abs/2604.10487