The search for a new model structure of β-Factor XIIa

We present the search for a new model of -factor XIIa, a blood coagulation enzyme, with an unknown experimental 3D-structure. We decided to build not one but three different models using different homologous proteins as well as different techniques and different modellers. Additional studies, including extensive molecular dynamics simulations on the solvated state, allowed us to draw several conclusions concerning homology modelling, in general, and -factor XIIa, in particular.     

(1-Adamantanethio)pyridines and tetrahydropyridines from the reaction of 1-adamantanethiol with pyridine I-oxide in acetic anhydride

The reaction of pyridine 1-oxide with 1-adamantanethiol in acetic anhydride produced a mixture of 2- and 3-(1-adamantanethio)pyridines, 1-aeetyl-2-(1-adamantanethio)-3-hydroxy-4-acetoxy-1,2,3,4-telrahydropyridine and the corresponding 3-acetoxyderivative. Pure substances were separated by means of column chromatography on alumina. The tetrahydropyridines were identified by means of their proton magnetic and mass spectra. 4-(1-Adamantanethio)pyridine was synthesized from 4-chloropyridinc and 1-adamantanethiol. The three isomeric (1-adamantanethio)-pyridines were, each, cleaved by concentrated hydrochloric acid to give 1-chloroadamantane and the corresponding pyridinethiol.     

Role of pyridine in the catalytic activation of sodium hypochlorite in the presence of manganese porphyrin

Steric and electronic influences of various substituted pyridines support the hypothesis of the coordination of pyridine in the manganese porphyrin-catalysed epoxidation of olefins with sodium hypochlorite solution.     

Calculation of Franck-Condon factors including anharmonicity: simulation of the C2H4+X2B3u<--C2H4X1A(g) band in the photoelectron spectrum of ethylene

Our new simple method for calculating accurate Franck-Condon factors including nondiagonal (i.e., mode-mode) anharmonic coupling is used to simulate the C2H4+X2B3u<--C2H4X1A(g) band in the photoelectron spectrum. An improved vibrational basis set truncation algorithm, which permits very efficient computations, is employed. Because the torsional mode is highly anharmonic it is separated from the other modes and treated exactly. All other modes are treated through the second-order perturbation theory. The perturbation-theory corrections are significant and lead to a good agreement with experiment, although the separability assumption for torsion causes the C2D4 results to be not as good as those for C2H4. A variational formulation to overcome this circumstance, and deal with large anharmonicities in general, is suggested.     

Energetic and topological analysis of the reaction of Mo and Mo2 with NH3, C2H2, and C2H4 molecules

The Density functional theory has been applied to characterize the structural features of Mo(1,2)-NH(3),-C(2)H(4), and -C(2)H(2) compounds. Coordination modes, geometrical structures, and binding energies have been calculated for several spin multiplets. It has been shown that in contrast to the conserved spin cases (Mo(1,2)-NH(3)), the interaction between Mo (or Mo(2)) and C(2)H(4) (or C(2)H(2)) are the low-spin (Mo-C(2)H(4) and -C(2)H(2)) and high-spin (Mo(2)-C(2)H(4) and -C(2)H(2)) complexes. In the ground state of Mo(1,2)-C(2)H(4) and -C(2)H(2), the metal-center always reacts with the C-C center. The spontaneous formation of the global minima is found to be possible due to the crossing between the potential energy surfaces (ground and excited states with respect to the metallic center). The bonding characterization has been performed using the topological analysis of the Electron Localization Function. It has been shown that the most stable electronic structure for a pi-acceptor ligand correlates with a maximum charge transfer from the metal center to the C-C bond of the unsaturated hydrocarbons, resulting in the formation of two new basins located on the carbon atoms (away from hydrogen atoms) and the reduction of the number of attractors of the C-C basin. The interaction between Mo(1,2) and C(2)H(4) (or C(2)H(2)) should be considered as a chemical reaction, which causes the multiplicity change. Contrarily, there is no charge transfer between Mo(1,2) and NH(3), and the partners are bound by an electrostatic interaction.     

Peroxisome Proliferator-Activated Receptors target family landscape: A chemometrical approach to ligand selectivity based on protein binding site analysis

The Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors which over the last couple of years have been the focus of considerable research efforts aiming to identify compounds with well-defined selectivity profiles for the treatment of metabolic diseases. The ligand binding domains (LBD) of the three known PPAR subtypes exhibit between 60 and 70% sequence identity. To gain insight into the structural determinants of selectivity for the PPAR subtypes, a set of 13 crystal structures of PPAR LBD were classified, using the GRID/CPCA approach. As a result, nearly all of the crystal structures of each different PPAR subtype were found clustered in different regions of the CPCA score plots, and hydrophobic as well as steric interactions were identified as the major determinants of PPAR subtypes selectivity. Furthermore, interpretation of the GRID/CPCA model in structural terms led to the identification of LBD regions which could be targeted to improve the selectivity for a given PPAR subtype. Our findings are consistent with published structure-activity relationships for PPAR ligands as well as with site-directed mutagenesis results.     

Harmonic analysis of large systems. II. Comparison of different protein models

A series of normal mode analyses of bovine pancreatic trypsin inhibitor (BPTI) has been performed. The results of modifying the long-range truncation of electrostatics, reducing the conformational space of the system (reduced basis normal mode analysis), and using different parameter sets and models for the potential function are reported. Both explicit (904 atoms) and polar hydrogen (580 atoms) representations of BPTI were examined and produced nearly identical normal mode vectors but slightly modified vibrational frequencies. The truncation methods—no cutoff, shift, and switch—were examined, and the use of a short switching function was found to alter harmonic motion greatly. A table relating the different cutoff methods to several previously published frequencies for BPTI indicates that the diversity of published lowest frequencies is due to the use of different electrostatic models rather than to inherent differences in the models or energy parameters. Examining reduced basis results demonstrates that a dihedral basis yields similar normal mode vectors, though the vibrational frequencies are shifted to higher values. The analysis of BPTI harmonic dynamics using a spherical harmonic reduced basis set yields significantly altered dynamics, indicating that BPTI is not well represented as a homogeneous object at low temperatures. © 1995 John Wiley & Sons, Inc.

1 This article is a U.S. Government work and, as such, is in the public domain in the United States of America.