A molecular orbital study of the conformation of formycin

Semiempirical quantum mechanical calculations, using the iterative extended Huckel theory, are carried out for the evaluation of conformational energies, dipole moment and net atomic charges as a function of the rotation about the glycosidic bond. Torsion about the C(4′)-C(5′) bond has also been considered. The energy diagrams for either the gg or gt rotamers of formycin predict that neither the first or the second energy minimum fall in the classical anti or syn regions. The predicted energy difference between the two most preferred conformations is rather large (3 kcal/mole). In contrast adenosine is predicted to favor the anti conformation by less than 1 kcal/mole. Barriers to internal counter-clockwise rotation about the glycosidic bond are higher for adenosine.     

A molecular orbital study of the conformation of barbiturates

The all-valence electrons molecular orbital method PCILO (Perturbative Configuration Interaction using Localized Orbitals) is applied to the study of the conformational and electronic properties of barbiturates. The results indicate the preference for specific conformations which correspond to a tendency for at least a partial folding of the aliphatic substituents towards the barbituric ring, and the eclipsing by the cyclic substituents of the bonds ending at C₅. The theoretical results agree with available experimental data from X-ray crystallography. On the other hand, the substituents at C₅ exert a negligible influence on the charge distribution in the barbituric ring. This situation agrees with the hypothesis that the factors responsible for the pharmacological activity of these drugs reside probably essentially in the electronic properties of the barbituric ring system (perhaps in its ability to hydrogen-bond with adenine), the role of the substituents at C₅ being mainly to favor the transfer of the drug to its receptors and the establishment of an appropriate contact with it.     

Coenzyme Q: a molecular orbital study.

The molecular structure and electronic properties of coenzyme Q, also known as ubiquinone, have been studied with the methods of semiempirical molecular orbital theory. It is found that the preferred conformation of the isoprene unit is such that formation of the chroman is favorable. The methoxy groups then assume a nonplanar configuration. Orbital energies, dipole moments, and spectra for the coenzyme Q₁ molecule and some of its chroman intermediates are also given in the calculations. The possibility of charge-transfer complex formation of chroman intermediate with inorganic phosphate is discussed.     

A molecular orbital study on the enzymic reaction mechanism of alpha-chymotrypsin

On the basis of the three-dimensional structure of the active site of α-chymotrypsin determined by X-ray diffraction analysis, we calculated a total energy and delocalization energy by using a molecular orbital method including all valence electrons, i.e. σ- and π-electrons. The calculated potential curve for a hydrolysis by a-chymotrypsin reproduced the experimental curve well, and the relative magnitudes of all steps in the reaction path explain the experimentally obtained activation energies satisfactorily. The validity of the “charge relay system” proposed by Blow and co-workers was investigated from the quantum-chemical point of view, and the possible importance of this structure for the acceleration of the hydrolysis through a proton transfer within the active site was pointed out. Delocalization energy was proved to play an important role in lowering the activation energy, and the effect of “orbital steering” suggested by Koshland and co-workers was also shown to be of importance for the catalytic reaction of α-chymotrypsin.     

A molecular mechanics and semiempirical molecular orbital study on the conformation of polynorbornene chains

The conformational analysis of polynorbornene (PNB) chains was investigated with the AM1, MM2, AMBER and OPLS methods taking into consideration the possibility of binding of norbornene monomers to each other at various positions, i.e. exo–exo, exo–endo, endo–endo. The chain that is formed by connecting exo–endo positions of the monomers has lower torsional barrier energy than those formed with bonds at other positions and has more flexibility. It is determined that the thredisyndiotactic chain formed by exo–endo addition adopts a helix structure and has a coil shape. The disyndiotactic chain formed by connecting norbornene monomers in mixed type has a linear structure. It is found that the repeat unit conformations of thredisyndiotactic and disyndiotactic chains of PNB are TGTG^– and (TGTG^–)₂, respectively.     

Bacteriorhodopsin (BR570) bathochromic band shift in an external electric field

In dry films of bacteriorhodopsin-containing purple membranes from Halobacterium halobium the external electric field (10⁴–10⁵ V · cm^?1) induces the appearance of a product spectrally close to the initial intermediate of bacteriorhodopsin (BR) photochromic cycle (batho form, K). This result and also preliminary data of the electret-thermal analysis of the preparations suggest that the dielectric polarization in chromophore-protein-lipid complexes might be an essential step of the primary stabilization of light energy in photo-bioenergetic processes.     

A molecular orbital study of stability and the conformation of double-stranded DNA-like polymers

The stacking and hydrogen bonding energies between bases in the B form of DNA were calculated by a perturbation method using the wave functions by the CNDO and the P-P-P methods. The exchange energies were calculated by using the corresponding orbitals. The magnitudes of the sums of the average stacking and hydrogen bonding energies per base pair of double-stranded DNA-like polymers are in good parallel with the melting temperatures of the polymers. The polymers containing I-C pairs are exceptions to this relation. Intrastrand stacking bases have the potential minimum at the distances of 2·8–3·7 Å. The minimum of stacking energy of double-stranded polymer for rotation of base pair around the helix axis exists near 36°. The deviation of the potential minimum from 36° seems to parallel the feature of the X-ray diffraction pattern of the polymer.     

Bacteriorhodopsin (BR570) bathochromic band shift in an external electric field.

In dry films of bacteriorhodopsin-containing purple membranes from Halobacterium halobium the external electric field (10(4) -- 10(5) V . cm-1) induces the appearance of a product spectrally close to the initial intermediate of bacteriorhodopsin (BR) photochromic cycle (bathoform, K). This result and also preliminary data of the electret-thermal analysis of the preparations suggest that the dielectric polarization in chromophore-protein-lipid complexes might be an essential step of the primary stabilization of light energy in photo-bioenergetic processes.     

A structural model for ovine rhodopsin

An experimentally testable structure for ovine rhodopsin has been modelled from a combination of several secondary-structure prediction methods. The proposed structure agrees well with available experimental data. The model envisages seven transmembrane segments that are largely, but not entirely, α-helical. The prediction of roughly adjacent regions of more irregular structure within these segments (which could introduce significant changes in helix pitch or rotation) may provide a good working model for considering the structural mobility of the protein.     

Involvement of two groups in reversal of the bathochromic shift of pharaonis phoborhodopsin by chloride at low pH

Pharaonis phoborhodopsin (ppR; or pharaonis sensory rhodopsin II, psRII) is a photophobic receptor of the halobacterium Natronobacterium pharaonis. Its lambdamax is at 496 nm, but upon acidification in the absence of chloride, lambdamax shifted to 522 nm. This bathochromic shift is thought to be caused by the protonation of Asp75, which corresponds to Asp85 of bacteriorhodopsin (bR). The D75N mutant, in which Asp75 was replaced by Asn, had its lambdamax at approximately 520 nm, supporting this mechanism for the bathochromic shift. A titration of the shift yielded a pKa of 3.5 for Asp75. In the presence of chloride, the spectral shifts were different: with a decrease in pH, a bathochromic shift was first observed, followed by a hypsochromic shift on further acidification. This was interpreted as: the disappearance of a negative charge by the protonation of Asp75 was compensated by the binding of chloride, but it is worthy to note that the binding requires the protonation of another proton-associable group other than Asp75. This is supported by the observation that in the presence of chloride, upon acidification, the lambdamax of D75N even showed a blue shift, showing that the protonation of a proton-associable group (pKa = 1.2) leads to the chloride binding that gives rise to a blue shift.     

A molecular model of cooperative binding of Ca2+ with rhodopsin molecules in photoreceptor membranes]

Kinetics of calcium binding by photoreceptor membranes of cattle retina in concentration Ca2+ 0.5 and 1.0.10(-5) M in 5 mM tris-HCl buffer, pH 7.4 at 37 degrees C has been studied. Such kinetics is of oscillating nature. Analysis of calcium binding process curves by photoreceptor membranes allow to conclude, that crystalline areas of rhodopsin (receptor domains) can be formed in the structure of photoreceptor membranes. Conformation states and structure of rhodopsin molecules Ca-binding sites in receptor domains depend on the presence of Ca2+ in the medium. The structure of rhodopsin molecules Ca-binding sites in receptor domain formed in the presence of Ca2+ in the medium was proposed. According to the Hodgkin and Huxley conception concerning the properties of Na(+)- and K(+)-channels, the receptor domain with such a structure of rhodopsin molecules Ca-binding sites can represent the conjugate system of Na(+)- and K(+)-channels. Molecular mechanisms of photoreceptor and nerve cells excitation was also proposed.     

A proposed model for rhodopsin in photoreceptor membranes

Transient electric birefringence studies have been made on bovine rhodopsin solubilized in the detergent lauryldimethylamine oxide from glutaraldehyde fixed rod outer segment (ROS) membranes. It was found that fixation caused no appreciable differences in the measured relaxation times when compared with unfixed ROS. On the basis of these findings a model for the orientation of rhodopsin in photoreceptor membranes is proposed which accounts for translational diffusion and two modes of rotational diffusion. The proposed model is related to a number of experimentally determined biophysical properties reported in the literature.     

A molecular orbital study on the oxidation of hydrogen donor molecules by peroxidase compound II

The electronic characteristics of some hydrogen donor substrate (phenol and aniline derivatives) for peroxidase reaction were calculated with the aid of the CNDO/2 and other methods. These results were compared with the experimental data concerning the rate of oxidation of these compounds by peroxidase and hydrogen peroxide. No simple relationship between the total or frontier electron densities on the oxygen or nitrogen atoms, or the lowest unoccupied orbital energies, and the rate of oxidation was found. It was, however, found that the logarithm of the rate of oxidation for the compounds studied correlates linearly with the highest occupied orbital energies. Based on these results, the mechanism of electron transfer from the substrate to compound II is discussed.     

A molecular orbital study of the metabolic pathway with hydroquinone intermediate from benzene as carcinogen

A possible metabolic activation pathway of benzenein vivo is the nonenzymatic oxidation of hydroquinone producedvia the cytochrome P-450-mediate two-step oxidation of benzene. The mechanism of the further oxidation of hydroquinone and the nature of the most reactive intermediate have not yet been clarified, although it is speculated that the intermediate isp-benzoquinone and/orp-benzosemiquinone. The theoretical result of using molecular orbital calculations (ab initio and CNDO/2 methods) indicates that although the mechanism of the nonenzymatic oxidation of hydroquinone cannot yet be determined, the intermediate is thep-benzosemiquinone anion radical. It is also suggested that active-oxygen species such as hydroxyl radical, which accelerates the nonenzymatic oxidation, play an important role in the metabolic pathway in question.     

An ab initio molecular orbital study on the characteristics of 8-hydroxyguanine

To investigate the mechanism by which the 8-hydroxyguanine residue in DNA affects the fidelity of DNA replication, the intrinsic properties of this modified base were investigated using an ab initio molecular orbital method. The most stable 8-hydroxyguanine form was revealed to be 6,8-diketo. The addition of an oxygen atom to the 8 position of a guanine base was shown to change the electrostatic potential of the molecule entirely and to give it a negative character. This effect may influence the local structure of 8-hydroxyguanine-containing DNA and the interaction with DNA polymerase, thereby resulting in infidelity of DNA replication.