Recommending Hartree–Fock Theory with London-Dispersion and Basis-Set-Superposition Corrections for the Optimization or Quantum Refinement of Protein Structures

We demonstrate the importance of
properly accounting for London
dispersion and basis-set-superposition error (BSSE) in quantum-chemical
optimizations of protein structures, factors that are often still
neglected in contemporary applications. We optimize a portion of an
ensemble of conformationally flexible lysozyme structures obtained
from highly accurate X-ray crystallography data that serve as a reliable
benchmark. We not only analyze root-mean-square deviations from the
experimental Cartesian coordinates, but also, for the first time,
demonstrate how London dispersion and BSSE influence crystallographic R factors. Our conclusions parallel recent recommendations
for the optimization of small gas-phase peptide structures made by
some of the present authors: Hartree–Fock theory extended with
Grimme’s recent dispersion and BSSE corrections (HF-D3-gCP)
is superior to popular density functional theory (DFT) approaches.
Not only are statistical errors on average lower with HF-D3-gCP, but
also the convergence behavior is much better. In particular, we show
that the BP86/6-31G* approach should not be relied upon as a black-box
method, despite its widespread use, as its success is based on an
unpredictable cancellation of errors. Using HF-D3-gCP is technically
straightforward, and we therefore encourage users of quantum-chemical
methods to adopt this approach in future applications.