1,721,017 research outputs found
A variational definition of electrostatic potential derived charges
No full textIn a recent work [Laio, A., VandeVondele, J., Rothlisberger, U. J. Phys. Chem. B2002106, 7300] a novel method has been proposed to define dynamical electrostatic potential derived (D-RESP) charges for systems described within a quantum mechanics/molecular mechanics (QM/MM) scheme. Here, we derive the analytic dependence of these charges on the quantum charge density and on the atomic positions. This variational property can be exploited for defining interaction potentials between the quantum and the classical subsystems that depend explicitly on the value of the D-RESP charges. Such potentials can be used for a multitude of different purposes, such as improving the computational efficiency of the electrostatic coupling between the QM and the MM subsystems and for defining a QM/MM analogue of the exclusion schemes commonly used in classical biomolecular force fields
Three- and four-center trans effects in triply bonded ditungsten complexes: An ab initio molecular dynamics study of compounds with stoichiometry W2Cl4(NHEt)(2)(PMe3)(2)
No full textWe have performed ab initio molecular dynamics simulations based on density functional theory to characterize the structural, electronic, and dynamic properties of the three major isomeric forms of the title compound. In agreement with experimental results, calculations with two different parametrizations of the exchange-correlation functional (BLYP and BP) both indicate the cis-C-2 form as the most stable isomer. The relative energies of the different forms are, however, small (less than or similar to1-2 kcal/mol), and the three compounds show overall very similar ground-state properties. Larger differences exist in their finite temperature behavior, which is dominated by the facile dissociation of one or both phosphine ligands. The calculated activation energies for phosphine dissociation differ clearly for the trans and the cis isomers and vary in the order trans much less than cis-C-2 less than or similar to cis-C-i. Analysis of the electronic structure of the transition states shows that the difference in activation energy between cis and trans isomers can be rationalized in terms of a classic trans effect caused by a molecular orbital spanning the three atomic centers N-W-P. The subtle difference between the two cis isomers, on the other hand, is likely due to an analogous four-center trans effect N-W-W-P which is mediated via metal-metal orbitals and involves ligands on both tungsten atoms
D-RESP: Dynamically generated electrostatic potential derived charges from quantum mechanics/molecular mechanics simulations
Full text linkA scheme is proposed for calculating electrostatic potential (ESP) derived charges from mixed quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations. These charges are fitted to the electrostatic field due to the quantum charge density evaluated on the MM atoms close to the QM system and are restrained to the corresponding Hirshfeld value by a quadratic penalty function. The D-RESP charges estimated by this procedure reproduce the field due to the charge density polarized by the environment and can be obtained as a function of time along a finite temperature molecular dynamics trajectory with essentially no computational overhead with respect to a standard QM/MM calculation. The fluctuation of the D-RESP values in a finite temperature run provide information about the importance of polarization effects and thus allow for a direct comparison of the relative performance of polarizable versus non polarizable point charge models. Moreover, the D-RESP charges estimated by this procedure can be used as a simple and straightforward indicator of the chemical state of the syste
Cis-trans isomerization in triply-bonded ditungsten complexes: A multitude of possible pathways
No full textWe have investigated different possible mechanisms for the cis-trans isomerization in triply bonded ditungsten complexes with stoichiometry W2Cl4(NHEt)(2)(PMe3)(2) using static density functional calculations as well as Car-Parrinello simulations. Our studies reveal an unexpected richness of possible reaction pathways that include both unimolecular and bimolecular mechanisms. Among the possible routes that have been identified are processes involving successive dissociation/reassociation of phosphine ligands, intramolecular chloride hopping, intertungsten phosphine exchange as well as numerous combinations of these basic reaction types. All pathways involve maximal activation barriers of less than 35 kcal/mol and include phosphine concentration dependent and independent routes. The energetically most favorable phosphine-dependent pathway is based on the dissociation/reassociation of phosphine ligands. This path is characterized by a maximal dissociation barrier of IS kcal/mol. The fastest alternative unimolecular route (with a maximal activation barrier of 24 kcal/mol) is based on a direct exchange of phosphine between the two metallic coordination centers. All the identified pathways, with the exception of a previously proposed internal flip mechanism that can be ruled out on energetic grounds, are competitive and may contribute in various combinations to the overall reaction rate. The identified isomerization mechanisms are fully consistent with the experimentally observed 3-state-kinetics and the dependence of the overall reaction rate on the excess concentration of phosphine which is demonstrated with a simplified kinetic model of the process
A Hamiltonian electrostatic coupling scheme for hybrid Car-Parrinello molecular dynamics simulations
No full textWe present a fully Hamiltonian and computationally efficient scheme to include the electrostatic effects due to the classical environment in a Car-Parrinello mixed quantum Mechanics/molecular mechanics (QM/MM) method. The polarization due to the MM atoms close to the quantum system is described by a Coulombic potential modified at short range. We show that the functional form of this potential has to be chosen carefully in order to obtain the correct interaction properties and to prevent an unphysical escape of the electronic density to the MM atoms (the so-called spill-out effect). The interaction between the QM system and the more distant MM atoms is modeled by a Hamiltonian term explicitly coupling the multipole moments of the quantum charge distribution with the classical point charges. Our approach remedies some of the well known deficiencies of current electrostatic coupling schemes in QM/MM methods, allowing molecular dynamics simulations of mixed systems within a fully consistent and energy conserving approach
Reaction mechanism of caspases: Insights from QM/MM Car-Parrinello simulations
No full textCaspases are fundamental targets for pharmaceutical interventions in a variety of diseases involving disregulated apoptosis. Here, we present a quantum mechanics/mol. mechanics Car-Parrinello study of key steps of the enzymic reaction for a representative member of this family, caspase-3. The hydrolysis of the acyl-enzyme complex is described at the d. functional (BLYP) level of theory while the protein frame and solvent are treated using the GROMOS96 force field. These calcns. show that the attack of the hydrolytic water mol. implies an activation free energy of .apprx.DFA ~ 19+-4 kcal/mol in good agreement with exptl. data and leads to a previously unrecognized gem-diol intermediate that can readily (DFA ~ 5+-3 kcal/mol) evolve to the enzyme products. Our findings assist in elucidating the striking difference in catalytic activity between caspases and other structurally well-characterized cysteine proteases (papains and cathepsins) and may help design novel transition-state analog inhibitors. [on SciFinder (R)]LCB
Copper binding sites in the C-terminal domain of mouse prion protein: a hybrid (QM/MM) molecular dynamics study
No full textWe present a hybrid QM/MM Car–Parrinello
molecular dynamics study of the
copper-loaded C-terminal domain of the
mouse prion protein. By means of a statistical
analysis of copper coordination in
known protein structures, we localized the
protein regions with the highest propensity
for copper ion binding. The identified
candidate structures were subsequently
refined via QM/MM simulations. Their
EPR characteristics were computed to
make contact with the experimental data
and to probe the sensitivity to structural
and chemical changes. Overall best agreement
with the experimental EPR data
(Van Doorslaer et al., J Phys Chem B
2001; 105: 1631–1639) and the information
currently available in the literature is
observed for a binding site involving
H187. Moreover, a reinterpretation of the
experimental proton hyperfine couplings
was possible in the light of the present
computational findings
Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations
No full textCaspases are fundamental targets for pharmaceutical interventions in a variety of diseases involving disregulated apoptosis. Here, we present a quantum mechanics/molecular mechanics Car-Parrinello study of key steps of the enzymatic reaction for a representative member of this family, caspase-3. The hydrolysis of the acyl-enzyme complex is described at the density functional (BLYP) level of theory while the protein frame and solvent are treated using the GROMOS96 force field. These calculations show that the attack of the hydrolytic water molecule implies an activation free energy of ca. DeltaF(A) approximately equal 19 +/- 4 kcal/mol in good agreement with experimental data and leads to a previously unrecognized gem-diol intermediate that can readily (DeltaF(A) approximately equal 5 +/- 3 kcal/mol) evolve to the enzyme products. Our findings assist in elucidating the striking difference in catalytic activity between caspases and other structurally well-characterized cysteine proteases (papains and cathepsins) and may help design novel transition-state analog inhibitors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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