Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

TL;DR

This study investigates the challenges of applying pure Kohn-Sham DFT to protein molecules, highlighting convergence issues due to vanishing HOMO-LUMO gaps and exploring solutions like solvent modeling.

Contribution

It systematically analyzes convergence problems in pure DFT calculations on proteins and proposes solvent charge modeling as a solution to improve stability.

Findings

Pure functionals often fail to converge for large protein systems.

Including explicit solvent molecules can increase the HOMO-LUMO gap.

Simple point charge models help achieve convergence with pure functionals.

Abstract

Self-consistency based Kohn-Sham density functional theory (KS-DFT) electronic structure calculations with Gaussian basis sets are reported for a set of 17 protein-like molecules with geometries obtained from the protein data bank. It is found that in many cases such calculations do not converge due to vanishing HOMO-LUMO gaps. A sequence of polyproline I helix molecules is also studied, and it is found that self-consistency calculations using pure functionals fail to converge for helices longer than six proline units. Since the computed gap is strongly correlated to the fraction of Hartree-Fock exchange, test calculations using both pure and hybrid density functionals are reported. The tested methods include the pure functionals BLYP, PBE, and LDA, as well as Hartree-Fock and the hybrid functionals BHandHLYP, B3LYP, and PBE0. The effect of including solvent molecules in the calculations is studied, and it is found that the inclusion of explicit solvent molecules around the protein fragment in many cases gives a larger gap, but that convergence problems due to vanishing gaps still occur in calculations with pure functionals. In order to achieve converged results, some modeling of the charge distribution of solvent water molecules outside the electronic structure calculation is needed. Representing solvent water molecules by a simple point charge distribution is found to give non-vanishing HOMO-LUMO gaps for the tested protein-like systems also for pure functionals.