Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U.
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.
†Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, U.K.
Daniel J
DJ
Cole
‡Theory and Simulation of Materials, École Polytechnique Fédérale de Lausanne, MXC 341, Station 12, CH-1015 Lausanne, Switzerland.
David D
DD
O'Regan
†Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, U.K.
Mike C
MC
Payne
Hubbard U; density functional theory; heme; metalloprotein; myoglobin