Definition of Aromaticity on the Basis of Molecular Orbital Localizability

A new quantitative measure is given to characterize the aromaticity of conjugated molecules. By definition the aromaticity index, A, is equal to the deviation from the unity of the average it-orbital localizability of the molecule. The localizability of molecular orbitals is defined according to Diner, Malrieu, Jordan and Claverie. Aromaticity indices were calculated for 21 homo- and heteroconjugated molecules using the CND0/2 method. The relationship between our index and some other ones is discussed. In addition, the role of d-orbitals in aromaticity and the relation of Hiickel\u27s 4n + 2 rule to our definition are analyzed

A wavefunction model to chemical bonding

In this paper we give a brief survey on some specific aspects of a wavefunction model for chemical bonding which are connected to or have been motivated in part by the work of the late Istvan Mayer and colleagues. After a brief description of the early wavefunction models as reflected in Mayer's works, naturally leading to electron densities, we discuss localized molecular orbitals, and summarize some of the early initiatives and applications. The concept of the Chemical Hamiltonian, as introduced by Mayer, its extensions and some classical and some more advanced connections will be discussed. The twofold motivating role of Mayer in the development of the earliest, ab initio level macromolecular linear scaling methods, giving proven "ab initio quality" protein energy results by the adjustable density matrix assembler method, and in some other molecular fragment advances will be also pointed out

Definition of Aromaticity on the Basis of Molecular Orbital Localizability

A new quantitative measure is given to characterize the aromaticity of conjugated molecules. By definition the aromaticity index, A, is equal to the deviation from the unity of the average it-orbital localizability of the molecule. The localizability of molecular orbitals is defined according to Diner, Malrieu, Jordan and Claverie. Aromaticity indices were calculated for 21 homo- and heteroconjugated molecules using the CND0/2 method. The relationship between our index and some other ones is discussed. In addition, the role of d-orbitals in aromaticity and the relation of Hiickel\u27s 4n + 2 rule to our definition are analyzed

Diffraction techniques and vibrational spectroscopy opportunities to characterise bones

From a histological point of view, bones that allow body mobility and protection of internal organs consist not only of different organic and inorganic tissues but include vascular and nervous elements as well. Moreover, due to its ability to host different ions and cations, its mineral part represents an important reservoir, playing a key role in the metabolic activity of the organism. From a structural point of view, bones can be considered as a composite material displaying a hierarchical structure at different scales. At the nanometre scale, an organic part, i.e. collagen fibrils and an inorganic part, i.e. calcium phosphate nanocrystals are intimately mixed to assure particular mechanical properties

Electrostatics in computer-aided drug design

Hydrogen bonds and charge-charge interactions, determined by molecular electrostatics, play essential role in biopolymer-ligand associations. Accordingly, electrostatics is crucial in the qualitative and quantitative characterisation of the binding of drugs to their target molecules. In the following, we will give an account on the role of molecular electrostatics in a drug design, laying emphasis on our own work. We will survey the most important computation methods of molecular electrostatic potentials, then outline basic aspects of molecular recognition: steric, electrostatic and hydrophobic complementarity. On the basis of the complementarity, we will also define molecular similarity and discuss various applications of these concepts to the treatment of protein-ligand interactions and a rational drug design. Special attention will be paid to a receptor mapping and to a comparative molecular field analysis, with some our recent applications. A further important point will be the molecular electrostatic field (potential gradient) as a hydrophobicity measure. We will argue that the hydrophobic complementarity and similarity can be treated on the basis of matching regions of the interacting molecules that are characterised by a similar magnitude of the electrostatic field. The concept of the electrostatic complementarity will be extended to enzyme-substrate interactions, providing a firm basis for the quantitative estimation of catalytic rate enhancement

Crystallization and preliminary X-ray analysis of porcine muscle prolyl oligopeptidase

Prolyl oligopeptidase from pig muscle has been crystallized in complex with an inhibitor, using PEG 8000 and calcium acetate as precipitants. The crystals are orthorombic and the space group is P212121 with cell dimensions a = 111.8, b = 101.8, c = 72.4 Å. The asymmetric unit contains a single chain of prolyl oligopeptidase, corresponding to a specific volume of 2.55 Å3 Da-1 and a solvent content of 52%. The observed diffraction pattern extends to 2.3 Å resolution and the native crystals are well suited for structural analysis by X-ray diffraction methods. © 1998 International Union of Crystallography Printed in Great Britain - all rights reserved

Role of electrostatics at the catalytic metal binding site in xylose isomerase action: Ca2+-inhibition and metal competence in the double mutant D254E/D256E

The catalytic metal binding site of xylose isomerase from Arthrobacter B3728 was modified by protein engineering to diminish the inhibitory effect of Ca2+ and to study the competence of metals on catalysis. To exclude Ca2+ from Site 2 a double mutant D254E/D256E was designed with reduced space available for binding. In order to elucidate structural consequences of the mutation the binary complex of the mutant with Mg2+ as well as ternary complexes with bivalent metal ions and the open-chain inhibitor xylitol were crystallized for x-ray studies. We determined the crystal structures of the ternary complexes containing Mg2+, Mn2+, and Ca2+ at 2.2 to 2.5 \uc5 resolutions, and refined them to R factors of 16.3, 16.6, and 19.1, respectively. We found that all metals are liganded by both engineered glutamates as well as by atoms O1 and O2 of the inhibitor. The similarity of the coordination of Ca2+ to that of the cofactors as well as results with Be2+ weaken the assumption that geometry differences should account for the catalytic noncompetence of this ion. Kinetic results of the D254E/D256E mutant enzyme showed that the significant decrease in Ca2+ inhibition was accompanied by a similar reduction in the enzymatic activity. Qualitative argumentation, based on the protein electrostatic potential, indicates that the proximity of the negative side chains to the substrate significantly reduces the electrostatic stabilization of the transition state. Furthermore, due to the smaller size of the catalytic metal site, no water molecule, coordinating the metal, could be observed in ternary complexes of the double mutant. Consequently, the proton shuttle step in the overall mechanism should differ from that in the wild type. These effects can account for the observed decrease in catalytic efficiency of the D254E/D256E mutant enzyme