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.Comment: 15 pages, 3 figures. Supplementary material 8 pages, 3 figures. This
version matches that accepted for J. Phys. Chem. Lett. on 10th May 201
