Quantum-Centric Alchemical Free Energy Calculations
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arXiv
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| Main Authors: | , , , , , , |
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| Format: | Preprint |
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2025
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| _version_ | 1866908422382813184 |
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| author | Bazayeva, Milana Li, Zhen Kaliakin, Danil Liang, Fangchun Shajan, Akhil Das, Susanta Merz Jr, Kenneth M. |
| author_facet | Bazayeva, Milana Li, Zhen Kaliakin, Danil Liang, Fangchun Shajan, Akhil Das, Susanta Merz Jr, Kenneth M. |
| contents | In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction method. This approach applies the Multistate Bennett Acceptance Ratio (MBAR) over a coupling parameter λ to smoothly transition the system from molecular mechanics (MM) (λ = 0) to a quantum mechanics (QM) (λ = 1) description. The resulting correction is then applied to the classically (MM) computed AFE to account for the more accurate QM treatment. The standard book-ending procedure uses AMBER to simulate the MM region, and QUICK, AMBER's default QM engine, to handle the QM region with either the Hartree-Fock (HF) method or density functional theory (DFT). In this work, we introduce a novel interface to QUICK, via sander, that enables CI simulations, and can operate in two ways: A) via PySCF backend to perform full configuration interaction (FCI) using conventional computing resources, B) quantum-centric sample-based quantum diagonalization (SQD) workflow via Qiskit which leverages both quantum hardware and post-processing on conventional computing resources for CI simulations. In this workflow QUICK performs most steps of the calculations, but at user-defined intervals, it redirects the computation to either FCI or SQD backend to get the CI result. We computed the book-end corrections for the hydration free energy (HFE) of three small organic molecules (ammonia, methane, and water) to benchmark the proposed approach and demonstrate how quantum-computers can be used in AFE calculations. We believe that this approach can be scaled to more complex systems like drug-receptor interactions in future studies. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2506_20825 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Quantum-Centric Alchemical Free Energy Calculations Bazayeva, Milana Li, Zhen Kaliakin, Danil Liang, Fangchun Shajan, Akhil Das, Susanta Merz Jr, Kenneth M. Chemical Physics Quantum Physics In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction method. This approach applies the Multistate Bennett Acceptance Ratio (MBAR) over a coupling parameter λ to smoothly transition the system from molecular mechanics (MM) (λ = 0) to a quantum mechanics (QM) (λ = 1) description. The resulting correction is then applied to the classically (MM) computed AFE to account for the more accurate QM treatment. The standard book-ending procedure uses AMBER to simulate the MM region, and QUICK, AMBER's default QM engine, to handle the QM region with either the Hartree-Fock (HF) method or density functional theory (DFT). In this work, we introduce a novel interface to QUICK, via sander, that enables CI simulations, and can operate in two ways: A) via PySCF backend to perform full configuration interaction (FCI) using conventional computing resources, B) quantum-centric sample-based quantum diagonalization (SQD) workflow via Qiskit which leverages both quantum hardware and post-processing on conventional computing resources for CI simulations. In this workflow QUICK performs most steps of the calculations, but at user-defined intervals, it redirects the computation to either FCI or SQD backend to get the CI result. We computed the book-end corrections for the hydration free energy (HFE) of three small organic molecules (ammonia, methane, and water) to benchmark the proposed approach and demonstrate how quantum-computers can be used in AFE calculations. We believe that this approach can be scaled to more complex systems like drug-receptor interactions in future studies. |
| title | Quantum-Centric Alchemical Free Energy Calculations |
| topic | Chemical Physics Quantum Physics |
| url | https://arxiv.org/abs/2506.20825 |