Computational studies on imidazole heme conformations

Abstract

Density functional theory computations of heme with ionized propionic acid groups, axially coordinated with two imidazoles, were performed for different mutual orientations of the imidazole planes. Environmental influences from water or protein were considered with a continuum dielectric medium by solving the Poisson equation. In vacuum, optimized geometries yielded imidazole-heme conformations where the NH groups of imidazoles are oriented toward the heme propionic groups in agreement with data from crystal structures of heme proteins. Conformational free-energy dependencies of the mutual orientation of axially ligated imidazoles calculated in protein (epsilon=10) and water (epsilon=80) environments confirmed the vacuum results, albeit the energy difference between the preferred and the 180 degrees opposite orientations of the imidazole ligand decreased from 3.84 kcal/mol in vacuum to 2.35 and 2.40 kcal/mol in protein and water, respectively. Two main factors determine the imidazole orientation: (1) the direct intramolecular electrostatic interactions of propionic groups with the polar NH groups of imidazole and (2) the electrostatic interaction of the total dipole moment of the imidazole-heme complex with the reaction field. In vacuum, only the first type of interaction is present, while in a dielectric medium the latter effect becomes competitive at high dielectric constant, resulting in a decrease of the orientational preference. Interestingly, the orientational preference of the imidazole axially ligated to heme becomes even more pronounced, if the negatively charged propionates are neutralized by counter charges that mimic salt bridges or protonation of the propionates.

Accurate redox potentials of mononuclear iron, manganese, and nickel model complexes*

“…The standard free energy of reduction can be calculated routinely using the thermodynamic cycle 34,35 describing the relation between the electron attachment process in vacuum [gas phase, (g)] and the corresponding reduction in solution (see Fig. 1).…”

Hydrogen Bonds and Hydrophobic Interactions of Porphyrins in Porphyrin-Containing Proteins

“…In our previous work we studied orientations of imidazoles axially *Address correspondence to this author at the Department of Chemistry, University of Belgrade, Belgrade, Serbia; Tel: +381113336605; E-mail: szaric@chem.bg.ac.rs coordinated to iron-porphyrin [15][16][17][18]. It was shown that the noncovalent interactions with the propionic groups are very important for the orientations of the imidazoles and that the conformations of the propionic groups have strong influence on these interactions [15,17].…”

“…Negatively charged propionic groups of heme porphyrin can make strong hydrogen bonds and these bonds can determine conformations of the groups. As it was mentioned above, the conformations of the propionic groups greatly influence the orientation of axially coordinated imidazoles [15,17]. We used a nonredundant database of the Protein Data Bank (PDB), with 3,398 protein chains to examine systematically the occurrence and the role of hydrogen bonds and hydrophobic interactions of porphyrins.…”

CH/π interactions in metal–porphyrin complexes with pyrrole and chelate rings as hydrogen acceptors

“…Among other factors, noncovalent interactions can also influence the properties of metalloporphyrins [5,[9][10][11]. Metalloporphyrins can form several types of noncovalent interactions, some of them involving extended π-system of a porphyrin.…”