Quantum harmonic free energies for biomolecules and nanomaterials

TL;DR

This paper introduces a computational method to estimate harmonic vibrational free energies of large biomolecules and nanomaterials at the quantum level, enabling more practical thermodynamic calculations.

Contribution

A novel, cost-effective approach for quantum mechanical estimation of harmonic free energies in large molecular systems.

Findings

Error per atom decreases with system size in nanocrystals

Vibrational free energies of protein-ligand complexes can be estimated quantum mechanically

Method enables routine thermodynamic calculations at the quantum level

Abstract

Obtaining the free energy of large molecules from quantum mechanical energy functions is a longstanding challenge. We describe a method that allows us to estimate, at the quantum mechanical level, the harmonic contributions to the thermodynamics of molecular systems of large size, with modest cost. Using this approach, we compute the vibrational thermodynamics of a series of diamond nanocrystals, and show that the error per atom decreases with system size in the limit of large systems. We further show that we can obtain the vibrational contributions to the binding free energies of prototypical protein-ligand complexes where the exact computation is too expensive to be practical. Our work raises the possibility of routine quantum mechanical estimates of thermodynamic quantities in complex systems.