paper. Issue date 2014 Apr 22. Freely available online through the PNAS open access option. PMC Copyright notice PMCID: PMC4000798  PMID: 24717844 Significance Heme-based metalloproteins play a central role in respiration by transporting and storing oxygen, a function that is inhibited by carbon monoxide. Density-functional theory has been unable to provide a complete description of the binding of these ligands to heme's central iron atom, predicting an unrealistically high relative affinity for carbon monoxide. Here, we solve this problem using dynamical mean-field theory in combination with linear-scaling density-functional theory, thus allowing for a simultaneous description of crucial quantum entanglement and protein discrimination effects in the ground-state of the oxygen-heme complex. By simulating the binding process within a 1,000-atom quantum-mechanical model of the myoglobin metalloprotein, we obtain a significantly improved description of its spectroscopic and energetic observables. Keywords: metalloprotein, strong correlation, optical absorption, quantum-mechanical simulation, natural bond orbitals Abstract We carry out a first-principles atomistic study of the electronic mechanisms of ligand binding and discrimination in the myoglobin protein. Electronic correlation effects are taken into account using one of the most advanced methods currently available, namely a linear-scaling density functional theory (DFT) approach wherein the treatment of localized iron 3d electrons is further refined using dynamical mean-field theory. This combination of methods explicitly accounts for dynamical and multireference quantum physics, such as valence and spin fluctuations, of the 3d electrons, while treating a significant proportion of the protein (more than 1,000 atoms) with DFT. The computed electronic structure of the myoglobin complexes and the nature of the Fe–O 2 bonding are validated against experimental spectroscopic observables. We elucidate and solve a long-

[1404.5547] Renormalization of myoglobin-ligand binding energetics by quantum many-body effects \contributor Accepted for publication in the Proceedings of the National Academy of Sciences of the United States of America (2014). \urlwww.pnas.org/cgi/doi/10.1073/pnas.1322966111 \issuedateIssue Date \issuenumberIssue Number # Renormalization of myoglobin-ligand binding energetics by quantum many-body effects Cédric WeberTheory and Simulation of Condensed Matter, King s College London, London WC2R 2LS, United KingdomThomas Young Centre, University College London, London WC1H 0AH, United Kingdom 1 2 Daniel J. ColeDepartment of Chemistry, Yale University, New Haven, CT 06520-8107Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom 3 4 David D. O’ReganSchool of Physics and the Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, IrelandTheory and Simulation of Materials, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland 5 6 Mike C. Payne 4 (2014) ###### Abstract We carry out a first-principles atomistic study of the electronic mechanisms of ligand binding and discrimination in the m