Density-functional molecular dynamics studies of biologically relevant iron and cobalt complexes with macrocyclic ligands

Constrained Density Functional Theory

“…18,19 The introduction of a fictitious dynamics for the orbitals in the Car-Parrinello approach 20 further reduces computational costs and has enabled density functional simulations of bioactive and reactive species. [21][22][23] The establishment of linear-response time-dependent DFT (LR-TDDFT) as a viable, and in principle exact, 24,25 formalism for obtaining excited states from DFT laid the groundwork for its routine application to excited states in organic compounds 26 and transition metal complexes. 27 Paired with a classical force field via QM/MM or ONIOM techniques, DFT and TDDFT have gained traction for computational modeling of systems once only accessible to classical simulation, such as enzymes 28 and chromophores strongly coupled to a solvent bath.…”

“…Thanks to its computational tractability, DFT has been at the forefront of efforts to extend the reach of quantum chemistry beyond the traditional realms of single-point energies and geometries in the gas phase. DFT is now routinely employed alongside spectroscopic and electrochemical analyses , and is invoked in the interpretation of novel organic and organometallic reactivity. , The favorable accuracy-to-cost ratio of approximate DFT for large systems has made it the method of choice for quantum chemical studies of biomolecular systems − and has enabled classical molecular dynamics simulations on high-dimensional Born–Oppenheimer potential energy surfaces (PES). , The introduction of a fictitious dynamics for the orbitals in the Car–Parrinello approach further reduces computational costs and has enabled density functional simulations of bioactive and reactive species. − …”

Multireference and Multiconfiguration Ab Initio Methods in Heme-Related Systems: What Have We Learned So Far?

“…Until now, density functional theory (DFT) has played the dominant role in the interplay of theoretical and experimental efforts toward achieving this requisite understanding of the chemistry of heme species. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Whereas DFT is appropriate for model systems, the enzymatic species require a combined quantum mechanical/molecular mechanical (QM/MM) approach, [19][20][21][22][23][24][25][26][27][28][29] using DFT as the QM method for describing the active species and MM force fields to account as realistically as possible for the effect of protein environment. Indeed, QM(DFT)/MM studies have appeared by now for many heme proteins, e.g., cytochrome P450, 30 cytochrome c peroxidase (CcP) and ascorbate peroxidase (APX), [31][32][33][34][35] catalase and catalase-peroxidase, [36][37][38][39] horseradish peroxidase (HRP), [40][41][42][43][44][45][46][47] nitric oxide synthase (NOS), ...…”

“…As such, understanding the structure and reactivity of heme proteins and enzymes has evolved to be an important area of bioinorganic chemistry. Until now, density functional theory (DFT) has played the dominant role in the interplay of theoretical and experimental efforts toward achieving this requisite understanding of the chemistry of heme species. − Whereas DFT is appropriate for model systems, the enzymatic species require a combined quantum mechanical/molecular mechanical (QM/MM) approach, − using DFT as the QM method for describing the active species and MM force fields to account as realistically as possible for the effect of protein environment. Indeed, QM(DFT)/MM studies have appeared by now for many heme proteins, e.g., cytochrome P450, cytochrome c peroxidase (C c P) and ascorbate peroxidase (APX), − catalase and catalase-peroxidase, − horseradish peroxidase (HRP), − nitric oxide synthase (NOS), − heme oxygenase (HO), , myoglobin (Mb) and hemoglobin (Hb), − truncated Hb, − chloroperoxidase (CPO), − and tryptophan/indoleamine 2,3-dioxygenase (TDO/IDO). − …”

Interactions of Hemoglobin and Myoglobin with Their Ligands CN–, CO, and O2 Monitored by Electrospray Ionization-Mass Spectrometry

“…Hemoglobin (Hb) serves as oxygen carrier in red blood cells. , In the physiologically active protein, each of the four subunits contains a ferrous heme iron (Fe II ) that is coordinated by a proximal histidine. Oxygen binding takes place at the opposite face of the heme, where O 2 can occupy the remaining coordination site while also forming a H-bond with a distal histidine. − The oxygen-saturated protein (with four O 2 bound) is referred to as HbO 2 . The allosteric nature of oxygen binding to Hb and the associated structural changes of the (αβ) 2 quaternary structure continue to be a topic of research. − Similarly, the changes in iron and oxygen electron configuration during binding remain under investigation. ,, …”