How to use quantum computers for biomolecular free energies

Fuente: arXiv
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Hauptverfasser: Günther, Jakob, Weymuth, Thomas, Bensberg, Moritz, Witteveen, Freek, Teynor, Matthew S., Thomasen, F. Emil, Sora, Valentina, Bro-Jørgensen, William, Husistein, Raphael T., Erakovic, Mihael, Miller, Marek, Weisburn, Leah, Cho, Minsik, Eckhoff, Marco, Harrow, Aram W., Krogh, Anders, Van Voorhis, Troy, Lindorff-Larsen, Kresten, Solomon, Gemma, Reiher, Markus, Christandl, Matthias
Format: Preprint
Veröffentlicht: 2025
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author Günther, Jakob
Weymuth, Thomas
Bensberg, Moritz
Witteveen, Freek
Teynor, Matthew S.
Thomasen, F. Emil
Sora, Valentina
Bro-Jørgensen, William
Husistein, Raphael T.
Erakovic, Mihael
Miller, Marek
Weisburn, Leah
Cho, Minsik
Eckhoff, Marco
Harrow, Aram W.
Krogh, Anders
Van Voorhis, Troy
Lindorff-Larsen, Kresten
Solomon, Gemma
Reiher, Markus
Christandl, Matthias
author_facet Günther, Jakob
Weymuth, Thomas
Bensberg, Moritz
Witteveen, Freek
Teynor, Matthew S.
Thomasen, F. Emil
Sora, Valentina
Bro-Jørgensen, William
Husistein, Raphael T.
Erakovic, Mihael
Miller, Marek
Weisburn, Leah
Cho, Minsik
Eckhoff, Marco
Harrow, Aram W.
Krogh, Anders
Van Voorhis, Troy
Lindorff-Larsen, Kresten
Solomon, Gemma
Reiher, Markus
Christandl, Matthias
contents Free energy calculations are at the heart of physics-based analyses of biochemical processes. They allow us to quantify molecular recognition mechanisms, which determine a wide range of biological phenomena from how cells send and receive signals to how pharmaceutical compounds can be used to treat diseases. Quantitative and predictive free energy calculations require computational models that accurately capture both the varied and intricate electronic interactions between molecules as well as the entropic contributions from motions of these molecules and their aqueous environment. However, accurate quantum-mechanical energies and forces can only be obtained for small atomistic models, not for large biomacromolecules. Here, we demonstrate how to consistently link accurate quantum-mechanical data obtained for substructures to the overall potential energy of biomolecular complexes by machine learning in an integrated algorithm. We do so using a two-fold quantum embedding strategy where the innermost quantum cores are treated at a very high level of accuracy. We demonstrate the viability of this approach for the molecular recognition of a ruthenium-based anticancer drug by its protein target, applying traditional quantum chemical methods. As such methods scale unfavorable with system size, we analyze requirements for quantum computers to provide highly accurate energies that impact the resulting free energies. Once the requirements are met, our computational pipeline FreeQuantum is able to make efficient use of the quantum computed energies, thereby enabling quantum computing enhanced modeling of biochemical processes. This approach combines the exponential speedups of quantum computers for simulating interacting electrons with modern classical simulation techniques that incorporate machine learning to model large molecules.
format Preprint
id arxiv_https___arxiv_org_abs_2506_20587
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle How to use quantum computers for biomolecular free energies
Günther, Jakob
Weymuth, Thomas
Bensberg, Moritz
Witteveen, Freek
Teynor, Matthew S.
Thomasen, F. Emil
Sora, Valentina
Bro-Jørgensen, William
Husistein, Raphael T.
Erakovic, Mihael
Miller, Marek
Weisburn, Leah
Cho, Minsik
Eckhoff, Marco
Harrow, Aram W.
Krogh, Anders
Van Voorhis, Troy
Lindorff-Larsen, Kresten
Solomon, Gemma
Reiher, Markus
Christandl, Matthias
Quantum Physics
Strongly Correlated Electrons
Biological Physics
Chemical Physics
Computational Physics
Free energy calculations are at the heart of physics-based analyses of biochemical processes. They allow us to quantify molecular recognition mechanisms, which determine a wide range of biological phenomena from how cells send and receive signals to how pharmaceutical compounds can be used to treat diseases. Quantitative and predictive free energy calculations require computational models that accurately capture both the varied and intricate electronic interactions between molecules as well as the entropic contributions from motions of these molecules and their aqueous environment. However, accurate quantum-mechanical energies and forces can only be obtained for small atomistic models, not for large biomacromolecules. Here, we demonstrate how to consistently link accurate quantum-mechanical data obtained for substructures to the overall potential energy of biomolecular complexes by machine learning in an integrated algorithm. We do so using a two-fold quantum embedding strategy where the innermost quantum cores are treated at a very high level of accuracy. We demonstrate the viability of this approach for the molecular recognition of a ruthenium-based anticancer drug by its protein target, applying traditional quantum chemical methods. As such methods scale unfavorable with system size, we analyze requirements for quantum computers to provide highly accurate energies that impact the resulting free energies. Once the requirements are met, our computational pipeline FreeQuantum is able to make efficient use of the quantum computed energies, thereby enabling quantum computing enhanced modeling of biochemical processes. This approach combines the exponential speedups of quantum computers for simulating interacting electrons with modern classical simulation techniques that incorporate machine learning to model large molecules.
title How to use quantum computers for biomolecular free energies
topic Quantum Physics
Strongly Correlated Electrons
Biological Physics
Chemical Physics
Computational Physics
url https://arxiv.org/abs/2506.20587