Quantum Computing Reveals Energetics of Tau Peptide Fragments

ABSTRACT Near-term quantum algorithms such as the variational quantum eigensolver (VQE) have been widely explored for small-molecule electronic structure calculations, yet their relevance for biologically motivated peptide systems remains largely untested. Here, we apply a rigorously controlled, fragment-based VQE workflow to a tau-derived peptide fragment implicated in protein aggregation in Alzheimer’s Disease. Using an identical active space, basis set, and frozen-core treatment, we benchmark VQE electronic energies against classical restricted Hartree-Fock (RHF) calculations and molecular dynamics (MD) force-field energies across an ensemble of peptide conformations. While VQE and active-space RHF energies show systematic agreement within the defined electronic subspace, both exhibit weak correlation with MD-derived energetics, highlighting the fundamentally different physical contributions captured by electronic structure methods and classical force fields. These results demonstrate that NISQ-era quantum chemistry provides complementary, rather than redundant, information relative to classical MD and delineate the scope and limitations of applying VQE to biologically relevant peptide fragments. Our study establishes a disease-motivated benchmark framework for integrating quantum electronic structure calculations with classical simulation approaches in peptide biophysics.