Fullqubit alchemist: Quantum algorithm for alchemical free energy calculations

TL;DR

This paper introduces a quantum algorithm that improves the efficiency of free energy calculations in biological systems, potentially transforming drug discovery by reducing computational costs and scaling better than classical methods.

Contribution

It presents a novel quantum algorithm that directly implements the Liouvillian approach and performs fully quantum thermodynamic integration, enhancing scalability and efficiency.

Findings

Super-polynomial runtime scaling improvements

Quadratic scaling with the number of particles

Elimination of entropy estimation subroutines

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.