Prediction of strong O-H/M hydrogen bonding between water and square-planar Ir and Rh complexes.

Intermolecular O-H/M interactions, between a water molecule and square-planar acac complexes ([M(acac)L2]), with different types of L ligands (en, H2O, CO, CN-, and OH-) and different types of metal atoms (Ir(i), Rh(i), Pt(ii), and Pd(ii)) were studied by high level ab initio calculations. Among the studied neutral complexes, the [Pd(acac)(CN)(CO)] complex forms the weakest interaction, -0.62 kcal mol-1, while the [Ir(acac)(en)] complex forms the strongest interaction, -9.83 kcal mol-1, which is remarkably stronger than the conventional hydrogen bond between two water molecules (-4.84 kcal mol-1).

Aliphatic-aromatic stacking interactions in cyclohexane-benzene are stronger than aromatic-aromatic interaction in the benzene dimer.

Stacking interactions between cyclohexane and benzene were studied in crystal structures from the Cambridge Structural Database and by ab initio calculations. Calculated at the very accurate CCSD(T)/CBS level of theory, the cyclohexane-benzene interaction energy is -3.27 kcal mol-1, which is significantly stronger than the interaction in the benzene dimer (-2.84 kcal mol-1) indicating the importance of aliphatic-aromatic interactions.

Factors determining the orientation of axially coordinated imidazoles in heme proteins.

Factors determining conformations of imidazole axially coordinated to heme in heme proteins were investigated by analyzing 693 hemes in 432 different crystal structures of heme proteins from the Protein Data Bank (PDB), where at least one histidine is ligated to heme. The results from a search of the PDB for protein structures were interpreted with molecular force field computations. Analysis of data from these crystal structures indicated that there are two main factors that determine the orientations of imidazole ligated to heme. These are the interactions of imidazole with the propionic acid side chains of heme and with the histidine backbone. From the analysis of the crystal structures of heme proteins, it turned out that the hydrogen bonding pattern is often not decisive, though it is probably used by nature to fine-tune the orientation of imidazole axially ligated to heme. We found that in many heme proteins the NdeltaH group of imidazole ligated to heme can assume a number of different hydrogen bonds and that in mutant structures the orientation of the ligated imidazole often does not change significantly, although the mutant altered the hydrogen bonding scheme involving the imidazole. Data from crystal structures of heme proteins show that there are preferred orientations of imidazoles with respect to heme. Generally, the NdeltaH group of imidazole is oriented toward the propionic acid groups of the heme. In some cases, the NdeltaH group of imidazole is close to only one of the propionic acid groups, but it is practically never oriented in the opposite direction. The imidazole also adopts a preferred orientation with respect to its histidine backbone such that the plane of the imidazole ring is practically never parallel to the Calpha-Cbeta bond of its histidine backbone. For a given conformation of histidine backbone with respect to heme, as well as imidazole with respect to histidine backbone, the orientation of the imidazole with respect to heme is uniquely determined, since the three orientations depend on each other. Hence, the interaction of the imidazole with the backbone also influences the orientation of the imidazole with respect to the heme. Force field computations are in agreement with experimental data. With this method, we showed that there is an energy minimum when the NdeltaH group of the imidazole is oriented toward the propionic acid groups and that there are minima of energy for orientations where the imidazole ring is orthogonal to the plane defined by the Calpha-Cbeta and Cbeta-Cgamma bonds of the histidine. The computations also demonstrated that these interactions are mainly of electrostatic origin. By taking into account these two major factors, we were able to understand the orientations of axially coordinated imidazoles for all groups of heme proteins, except for the group of cytochrome c peroxidase. In this group, the orientation of the imidazole is determined by a strong hydrogen bond of the NdeltaH group with Asp235.

Artificial cytochrome b: computer modeling and evaluation of redox potentials.

We generated atomic coordinates of an artificial protein that was recently synthesized to model the central part of the native cytochrome b (Cb) subunit consisting of a four-helix bundle with two hemes. Since no X-ray structure is available, the structural elements of the artificial Cb were assembled from scratch using all known chemical and structural information available and avoiding strain as much as possible. Molecular dynamics (MD) simulations applied to this model protein exhibited root-mean-square deviations as small as those obtained from MD simulations starting with the crystal structure of the native Cb subunit. This demonstrates that the modeled structure of the artificial Cb is relatively rigid and strain-free. The model structure of the artificial Cb was used to determine the redox potentials of the two hemes by calculating the electrostatic energies from the solution of the linearized Poisson-Boltzmann equation (LPBE). The calculated redox potentials agree within 20 meV with the experimentally measured values. The dependence of the redox potentials of the hemes on the protein environment was analyzed. Accordingly, the total shift in the redox potentials is mainly due to the low dielectric medium of the protein, the protein backbone charges, and the salt bridges formed between the arginines and the propionic acid groups of the hemes. The difference in the shift of the redox potentials is due to the interactions with the hydrophilic side chains and the salt bridges formed with the propionic acids of the hemes. For comparison and to test the computational procedure, the redox potentials of the two hemes in the native Cb from the cytochrome bc(1) (Cbc(1)) complex were also calculated. Also in this case the computed redox potentials agree well with experiments.

Metal ligand aromatic cation-pi interactions in metalloproteins: ligands coordinated to metal interact with aromatic residues.

Cation-pi interactions between aromatic residues and cationic amino groups in side chains and have been recognized as noncovalent bonding interactions relevant for molecular recognition and for stabilization and definition of the native structure of proteins. We propose a novel type of cation-pi interaction in metalloproteins; namely interaction between ligands coordinated to a metal cation--which gain positive charge from the metal--and aromatic groups in amino acid side chains. Investigation of crystal structures of metalloproteins in the Protein Data Bank (PDB) has revealed that there exist quite a number of metalloproteins in which aromatic rings of phenylalanine, tyrosine, and tryptophan are situated close to a metal center interacting with coordinated ligands. Among these ligands are amino acids such as asparagine, aspartate, glutamate, histidine, and threonine, but also water and substrates like ethanol. These interactions play a role in the stability and conformation of metalloproteins, and in some cases may also be directly involved in the mechanism of enzymatic reactions, which occur at the metal center. For the enzyme superoxide dismutase, we used quantum chemical computation to calculate that Trp163 has an interaction energy of 10.09 kcal mol(-1) with the ligands coordinated to iron.