Fullqubit alchemist: Quantum algorithm for alchemical free energy calculations

• URL: http://arxiv.org/abs/2508.16719v1
• Date: Fri, 22 Aug 2025 18:00:01 GMT
• Title: Fullqubit alchemist: Quantum algorithm for alchemical free energy calculations
• Authors: Po-Wei Huang, Gregory Boyd, Gian-Luca R. Anselmetti, Matthias Degroote, Nikolaj Moll, Raffaele Santagati, Michael Streif, Benjamin Ries, Daniel Marti-Dafcik, Hamza Jnane, Sophia Simon, Nathan Wiebe, Thomas R. Bromley, Bálint Koczor,
• Abstract summary: Accurately computing the free energies of biological processes is a cornerstone of computer-aided drug design.<n> classical methods, such as thermodynamic integration and alchemical free energy calculations, have significantly contributed to reducing computational costs.<n>We tackle this through a quantum algorithm for the estimation of free energy differences by adapting the existing Liouvillian approach.
• Score: 2.400139599287897
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: Accurately computing the free energies of biological processes is a cornerstone of computer-aided drug design but it is a daunting task. The need to sample vast conformational spaces and account for entropic contributions makes the estimation of binding free energies very expensive. While classical methods, such as thermodynamic integration and alchemical free energy calculations, have significantly contributed to reducing computational costs, they still face limitations in terms of efficiency and scalability. We tackle this through a quantum algorithm for the estimation of free energy differences by adapting the existing Liouvillian approach and introducing several key algorithmic improvements. We directly implement the Liouvillian operator and provide an efficient description of electronic forces acting on both nuclear and electronic particles on the quantum ground state potential energy surface. This leads to super-polynomial runtime scaling improvements in the precision of our Liouvillian simulation approach and quadratic improvements in the scaling with the number of particles. Second, our algorithm calculates free energy differences via a fully quantum implementation of thermodynamic integration and alchemy, thereby foregoing expensive entropy estimation subroutines used in prior works. Our results open new avenues towards the application of quantum computers in drug discovery.

Related papers

• Quantum-classical algorithm for Ewald summation based computation of long-range electrostatics [0.0]
  We propose a quantum algorithm for computation of Coulomb electrostatic energy for a system of point charges.<n>The algorithm can be implemented in running the all-atom Molecular Dynamics simulations on a quantum computer.
  arXiv  Detail & Related papers  (2025-12-24T02:06:04Z)
• Variational Quantum Subspace Construction via Symmetry-Preserving Cost Functions [39.58317527488534]
  We propose a variational strategy based on symmetry-preserving cost functions to iteratively construct a reduced subspace for extraction of low-lying energy states.<n>As a proof of concept, we test the proposed algorithms on H4 chain and ring, targeting both the ground-state energy and the charge gap.
  arXiv  Detail & Related papers  (2024-11-25T20:33:47Z)
• Towards Energetic Quantum Advantage in Trapped-Ion Quantum Computation [0.0]
  In this work, one implementation of the quantum Fourier transform (QFT) algorithm in a trapped ion setup was studied. The main focus was to obtain a theoretical characterization of the energetic costs of quantum computation. A potential scaling of the energetic costs was argued and used to find a possible threshold for an energetic quantum advantage against state-of-the-art classical supercomputers.
  arXiv  Detail & Related papers  (2024-04-17T17:14:53Z)
• Solving reaction dynamics with quantum computing algorithms [42.408991654684876]
  We study quantum algorithms for response functions, relevant for describing different reactions governed by linear response.<n>We focus on nuclear-physics applications and consider a qubit-efficient mapping on the lattice, which can efficiently represent the large volumes required for realistic scattering simulations.
  arXiv  Detail & Related papers  (2024-03-30T00:21:46Z)
• Folded Spectrum VQE : A quantum computing method for the calculation of molecular excited states [0.0]
  Folded Spectrum (FS) method as extension to Variational Quantum Eigensolver (VQE) algorithm for computation of molecular excited states. Inspired by the variance-based methods from the Quantum Monte Carlo literature, the FS method minimizes the energy variance, thus requiring a computationally expensive squared Hamiltonian. We apply the FS-VQE method to small molecules for a significant reduction of the computational cost.
  arXiv  Detail & Related papers  (2023-05-08T15:34:56Z)
• Quantum Thermal State Preparation [39.91303506884272]
  We introduce simple continuous-time quantum Gibbs samplers for simulating quantum master equations. We construct the first provably accurate and efficient algorithm for preparing certain purified Gibbs states. Our algorithms' costs have a provable dependence on temperature, accuracy, and the mixing time.
  arXiv  Detail & Related papers  (2023-03-31T17:29:56Z)
• Near-term quantum algorithm for computing molecular and materials properties based on recursive variational series methods [44.99833362998488]
  We propose a quantum algorithm to estimate the properties of molecules using near-term quantum devices. We test our method by computing the one-particle Green's function in the energy domain and the autocorrelation function in the time domain.
  arXiv  Detail & Related papers  (2022-06-20T16:33:23Z)
• A perspective on the current state-of-the-art of quantum computing for drug discovery applications [43.55994393060723]
  Quantum computing promises to shift the computational capabilities in many areas of chemical research by bringing into reach currently impossible calculations. We briefly summarize and compare the scaling properties of state-of-the-art quantum algorithms. We provide novel estimates of the quantum computational cost of simulating progressively larger embedding regions of a pharmaceutically relevant covalent protein-drug complex.
  arXiv  Detail & Related papers  (2022-06-01T15:05:04Z)
• Optimizing Electronic Structure Simulations on a Trapped-ion Quantum Computer using Problem Decomposition [41.760443413408915]
  We experimentally demonstrate an end-to-end pipeline that focuses on minimizing quantum resources while maintaining accuracy. Using density matrix embedding theory as a problem decomposition technique, and an ion-trap quantum computer, we simulate a ring of 10 hydrogen atoms without freezing any electrons. Our experimental results are an early demonstration of the potential for problem decomposition to accurately simulate large molecules on quantum hardware.
  arXiv  Detail & Related papers  (2021-02-14T01:47:52Z)
• Benchmarking adaptive variational quantum eigensolvers [63.277656713454284]
  We benchmark the accuracy of VQE and ADAPT-VQE to calculate the electronic ground states and potential energy curves. We find both methods provide good estimates of the energy and ground state. gradient-based optimization is more economical and delivers superior performance than analogous simulations carried out with gradient-frees.
  arXiv  Detail & Related papers  (2020-11-02T19:52:04Z)
• Quantum computing enhanced computational catalysis [2.285928372124628]
  We present an analysis of accurate energy measurements on a quantum computer for computational magnitude. New quantum algorithms for double-factorized representations of the four-indexs can significantly reduce the computational cost. We discuss the challenges of increasing active space sizes to accurately deal with dynamical correlations.
  arXiv  Detail & Related papers  (2020-07-28T20:07:43Z)
• Considerations for evaluating thermodynamic properties with hybrid quantum-classical computing work-flows [0.0]
  Quantum chemistry applications on quantum computers currently rely heavily on the variational quantum eigensolver algorithm. We present a summary of the hybrid quantum-classical work-flow to compute thermodynamic properties. We show that through careful selection of work-flow options, nearly order-of-magnitude increases in accuracy are possible at equivalent computing time.
  arXiv  Detail & Related papers  (2020-03-04T19:32:53Z)
• Simulation of Thermal Relaxation in Spin Chemistry Systems on a Quantum Computer Using Inherent Qubit Decoherence [53.20999552522241]
  We seek to take advantage of qubit decoherence as a resource in simulating the behavior of real world quantum systems. We present three methods for implementing the thermal relaxation. We find excellent agreement between our results, experimental data, and the theoretical prediction.
  arXiv  Detail & Related papers  (2020-01-03T11:48:11Z)

This list is automatically generated from the titles and abstracts of the papers in this site.

This site does not guarantee the quality of this site (including all information) and is not responsible for any consequences.