Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U

Abstract

Myoglobin modulates the binding of diatomic molecules to its heme group via hydrogen-bonding and steric interactions with neighboring residues, and is an important benchmark for computational studies of biomolecules. We have performed calculations on the heme binding site and a significant proportion of the protein environment (more than 1000 atoms) using linear-scaling density functional theory and the DFT+U method to correct for self-interaction errors associated with localized 3d states. We confirm both the hydrogen-bonding nature of the discrimination effect (3.6 kcal/mol) and assumptions that the relative strain energy stored in the protein is low (less than 1 kcal/mol). Our calculations significantly widen the scope for tackling problems in drug design and enzymology, especially in cases where electron localization, allostery or long-ranged polarization influence ligand binding and reaction.

15 pages, 3 figures. Supplementary material 8 pages, 3 figures. This version matches that accepted for J. Phys. Chem. Lett. on 10th May 2012

References in corpus (5)

• Density functional theory in transition-metal chemistry: a self-consistent Hubbard U approach
• Nearsightedness of Electronic Matter
• Accurate ionic forces and geometry optimisation in linear scaling density-functional theory with local orbitals
• Electrostatic Interactions in Finite Systems treated with Periodic Boundary Conditions: Application to Linear-Scaling Density Functional Theory
• Linear-scaling DFT+U with full local orbital optimization

Cited by in corpus (6)

• Electrostatic considerations affecting the calculated HOMO-LUMO gap in protein molecules
• The role of spin in the calculation of Hubbard $U$ and Hund's $J$ parameters from first principles
• Renormalization of myoglobin-ligand binding energetics by quantum many-body effects
• Importance of many body effects in the kernel of hemoglobin for ligand binding
• TDDFT+$U$: Hubbard corrected approximate density-functional theory in the excited-state regime
• Inapplicability of exact constraints and a minimal two-parameter generalization to the DFT+$U$ based correction of self-interaction error