Statistical replacement for systems with delta-correlated fluctuations

Nonlinear systems with stochastic parameters are approximated by simpler systems using a method that we call statistical replacement. This method is an extension of the previously developed AGREE which was restricted to systems with additive fluctuations. Statistical replacement incorporates the distinctions between globally stable thermodynamically closed systems and thermodynamically open systems that can be unstable.     

Heat conductivity of three periodic Hard Disks via nonequilibrium molecular dynamics

We use a driving field, of the type first suggested by Evans, to generate a steady heat current in the simplest possible system, a two-dimensional periodic fluid of three hard disks. Hard-disk motion equations can be conveniently derived from repulsive constant-force or linear-force potentials by considering the infinitely repulsive limit of these potentials. We show that the isoenergetic and isokinetic forms of the nonequilibrium equations of motion generate steady-state heat conductivities differing by terms of order 1/N, whereN is the number of particles. The resulting conductivities appear to vary as the logarithm of the driving field strength. Even at low fields, the three-body periodic-system results lie well below Enskog's infinite-system prediction.     

Own N-layered integrated molecular orbital and molecular mechanics study of the reaction of OH<Superscript>−</Superscript> with polychlorinated hydrocarbons CH<Subscript>(4−n)</Subscript>Cl<Subscript>n</Subscript> (n=2–4)

The reliability of the two-layer own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method was examined for the S_N2 reaction CH_(4–n)Cl_n+OH^–. In the ONIOM calculation, only the methyl chloride and OH^–were treated at a high level and the effect of polychlorination was taken into account only at a low level. The ONIOM results were compared with the target CCSD(T)/aug-cc-pVDZ//MP2/aug-cc-pVDZ results obtained by Borisov etal. [(2001) J. Phys. Chem. A 105:7724]. The ONIOM[MP2/aug-cc-pVDZ:B3LYP/6-31+G(d)] was found to reproduce well the target geometry and energy at the MP2/aug-cc-pVDZ level. The single-point improved energetics at the ONIOM[CCSD(T)/aug-cc-pVDZ:MP2/6-31+G(d)] is found to give results nearly as accurate as the target CCSD(T)/aug-cc-pVDZ//MP2/aug-cc-pVDZ results. The substantially reduced cost, 20% for optimization and 5% for single-point improved energy of the target cost for n=4, as well as small errors suggest that ONIOM is a powerful tool for accurate potential-energy surfaces of the reaction of large polyhalohydrocarbons.     

Intramolecular charge transfer in pyrromethene laser dyes: photophysical behaviour of PM650.

Absorption and fluorescence (steady-state and time-correlated) techniques are used to study the photophysical characteristics of the pyrromethene 650 (PM650) dye. The presence of the cyano group at the 8 position considerably shifts the absorption and fluorescence bands to lower energies with respect to other related pyrromethene dyes; this is attributed to the strong electron-acceptor character of the cyano group, as is theoretically confirmed by quantum mechanical methods. The fluorescence properties of PM650 are intensively solvent-dependent. The fluorescence band is shifted to lower energies in polar/protic solutions, and the evolution of the corresponding wavelength with the solvent is analysed by a multicomponent linear regression. The fluorescence quantum yield and the lifetime strongly decrease in polar/protic solvents, which can be ascribed to an extra nonradiative deactivation, via an intramolecular charge-transfer state (ICT state), favoured in polar media.     

A molecular modelling study of the interaction of noradrenaline with theβ 2-adrenergic receptor

Summary A model of the ₂-adrenergic receptor binding site is built from the primary structure of the receptor, experimental evidence for key binding residues and analogy with a homologous protein of partially determined structure. It is suggested that residues Trp-109, Thr-110 and Asp-113 are involved in ligand binding. Noradrenaline is successfully docked into this model, and the results of an INDO molecular orbital calculation on the complex indicate that a charge transfer interaction between Trp-109 and noradrenaline is possible.     

Computational study on the ring distortions of 1,4-dicyanobenzene in the gas phase and in the crystal

A molecular mechanics software enhanced to perform empirical energy calculations on crystals (KESSHOU) was further developed to handle intermolecular electrostatic interactions as well. The packing of the molecules of 1,4-dicyanobenzene and 1,4-diisocyanobenzene in the crystal was studied. The role of the van der Waals and the electrostatic interactions in the balance of nonbonded atom-atom interactions is analyzed. The packing forces are dominated by van der Waals forces. The electrostatic interactions have higher stabilizing contribution for the dicyano isomer than for the diisocyano form. The dependence of the results on the size of the crystal, the molecular mechanics force field (MM2 vs MM3), and the dielectric constant are also assessed. Ab initio MP2/6–311G** geometries of the isolated molecules are in accordance with the observed benzene ring distortions determined by electron diffraction.     

Complete-active-space self-consistent-field/Amber parameterization of the Lys296–retinal–Glu113 rhodopsin chromophore-counterion system

A special hybrid quantum mechanics/molecular mechanics forcefield is defined, parameterized and validated for studying the photoisomerization path of the retinal chromophore in the rhodopsin protein. It couples a multireference ab initio Hamiltonian (CASSCF and second-order multireference many-body perturbation theory using a CASSCF reference) to describe the chromophore while the rest of the protein is approximated with the Amber forcefield. The frontier has been carefully parameterized in order to reproduce full quantum mechanics torsional energy profiles, for both the ground state and the first excited state. It is also shown that replacing the chromophore counterion with point charges is a valid approximation. This result is interpreted in terms of a cancellation effect for which a possible explanation is given.     

Molecular modeling of intercalation complexes of antitumor active 9-aminoacridine and a [d,e]-anellated isoquinoline derivative with base paired deoxytetranucleotides

Summary Intercalators are molecules capable of sliding between DNA base pairs without breaking up the hydrogen bonds between the DNA bases. On the basis of molecular mechanics calculations structural, models of B-DNA tetranucleotide intercalation complexes of some cytostatic active 9-aminoacridines and of a [d, e]-anellated isoquinoline derivative are presented. The drug complexes are stabilized by energetically favouredvan der Waals interactions and by selective hydrogen bonds between the side chains of the drugs and the DNA bases. Semiempirical quantum chemistry calculations revealed that the chromophoric system of the intercalators is able to form ,-charge-transfer interactions with the purine bases of the base paired deoxytetranucleotides. The theoretical findings are of interest for a more specific drug design of cytostatically active agents.

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Molecular Modeling von Interkalationskomplexen antitumoraktiver 9-Aminoacridine sowie eines [d, e]-anellierten Isochinolinderivates mit basengepaarten Desoxytetranukleotiden

Zusammenfassung Interkalatoren sind Moleküle, die in der Lage sind, sich zwischen DNA-Basenpaare einzulagern, ohne die Wasserstoffbrücken zwischen den DNA-Basen aufzubrechen. Auf der Basis von molekülmechanischen Rechnungen werden Tetranukleotid-Interkalationskomplexe von verschiedenen zytostatisch aktiven 9-Aminoacridinen und von einem [d, e]-anellierten Isochinolinderivat präsentiert. Die Komplexe werden durch energetisch günstigevan der Waals-Interaktionen sowie durch selektive Wasserstoffbrückenbindungen zwischen den Seitenketten der Wirkstoffe und den DNA-Basen stabilisiert. Semiempirische quantenchemische Rechnungen ergaben, daß der Chromophor der Interkalatoren in der Lage ist, ,-charge-transfer Wechselwirkungen mit den Purinbasen der basengepaarten Desoxytetranukleotide auszubilden. Die theoretischen Ergebnisse sind für ein spezifischeres Wirkstoffdesign zytostatisch aktiver Verbindungen von Interesse.

     

Reverse-docking as a computational tool for the study of asymmetric organocatalysis

A novel methodology for 'reverse-docking' a cationic peptide-based organocatalyst to a rigid anionic transition state (TS) model for the conjugate addition of azide to alpha,beta-unsaturated carbonyl substrates is described. The resulting docking poses serve as simplified TS models for enantioselective catalysis. Molecular mechanics-based scoring and ranking of the docking poses, followed by clustering and structural analysis, reveal a clear energetic preference for docking to the S-enantiomeric azidation TS model, in agreement with experiment. Clear energetic trends emerged from docking the catalyst to both enantiomers of all six azidation TS models of this study. Structural analysis of the most favorable pose suggests a mechanism for enantioselective catalysis that is consistent with principles of molecular recognition, catalysis, and experimental data.