Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U

TL;DR

This study uses linear-scaling DFT+U to analyze ligand discrimination in myoglobin, confirming hydrogen-bonding effects and low strain energy, thereby expanding computational approaches in biomolecular research.

Contribution

It applies linear-scaling DFT+U to large biomolecular systems, providing new insights into ligand discrimination mechanisms in myoglobin.

Findings

Hydrogen-bonding contributes 3.6 kcal/mol to ligand discrimination.

Protein strain energy involved in ligand binding is less than 1 kcal/mol.

Method enables analysis of large biomolecules with localized electron effects.

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.