Towards the Simulation of Large Scale Protein-Ligand Interactions on NISQ-era Quantum Computers

TL;DR

This paper introduces a hybrid quantum-classical approach using symmetry-adapted perturbation theory with VQE to accurately compute large molecular interaction energies on NISQ-era quantum computers, reducing quantum resource requirements.

Contribution

It presents SAPT(VQE), a novel method combining symmetry-adapted perturbation theory with VQE, enabling efficient large-scale protein-ligand interaction simulations on near-term quantum devices.

Findings

SAPT(VQE) yields sub kcal/mol accuracy even with low-depth VQE.

Quantum resource requirements are reduced by computing on separate molecules.

Benchmarking shows promising results on small systems and a protein-related system.

Abstract

We explore the use of symmetry-adapted perturbation theory (SAPT) as a simple and efficient means to compute interaction energies between large molecular systems with a hybrid method combing NISQ-era quantum and classical computers. From the one- and two-particle reduced density matrices of the monomer wavefunctions obtained by the variational quantum eigensolver (VQE), we compute SAPT contributions to the interaction energy [SAPT(VQE)]. At first order, this energy yields the electrostatic and exchange contributions for non-covalently bound systems. We empirically find from ideal statevector simulations that the SAPT(VQE) interaction energy components display orders of magnitude lower absolute errors than the corresponding VQE total energies. Therefore, even with coarsely optimized low-depth VQE wavefunctions, we still obtain sub kcal/mol accuracy in the SAPT interaction energies. In SAPT(VQE), the quantum requirements, such as qubit count and circuit depth, are lowered by performing computations on the separate molecular systems. Furthermore, active spaces allow for large systems containing thousands of orbitals to be reduced to a small enough orbital set to perform the quantum portions of the computations. We benchmark SAPT(VQE) (with the VQE component simulated by ideal state-vector simulators) against a handful of small multi-reference dimer systems and the iron center containing human cancer-relevant protein lysine-specific demethylase 5 (KDM5A).