Daniel Cole

Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U

Daniel J. Cole,1 David D. O'Regan,2 Mike C. Payne,1
1Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
2Theory and Simulation of Materials, Ecole Polytechnique Federale de Lausanne, MXC 341, Station 12, CH-1015 Lausanne, Switzerland

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.

Journal of Physical Chemistry Letters, 3, 1448 (2012)