43,412 research outputs found
Automated transition state theory calculations for high-throughput kinetics
A scarcity of known chemical kinetic parameters leads to the use of many
reaction rate estimates, which are not always sufficiently accurate, in the
construction of detailed kinetic models. To reduce the reliance on these
estimates and improve the accuracy of predictive kinetic models, we have
developed a high-throughput, fully automated, reaction rate calculation method,
AutoTST. The algorithm integrates automated saddle-point geometry search
methods and a canonical transition state theory kinetics calculator. The
automatically calculated reaction rates compare favorably to existing estimated
rates. Comparison against high level theoretical calculations show the new
automated method performs better than rate estimates when the estimate is made
by a poor analogy. The method will improve by accounting for internal rotor
contributions and by improving methods to determine molecular symmetry.Comment: 29 pages, 8 figure
Dynamic treatment of vibrational energy relaxation in a heterogeneous and fluctuating environment
A computational approach to describe the energy relaxation of a
high-frequency vibrational mode in a fluctuating heterogeneous environment is
outlined. Extending previous work [H. Fujisaki, Y. Zhang, and J.E. Straub, J.
Chem. Phys. {\bf 124}, 144910 (2006)], second-order time-dependent perturbation
theory is employed which includes the fluctuations of the parameters in the
Hamiltonian within the vibrational adiabatic approximation. This means that the
time-dependent vibrational frequencies along an MD trajectory are obtained via
a partial geometry optimization of the solute with fixed solvent and a
subsequent normal mode calculation. Adopting the amide I mode of
N-methylacetamide in heavy water as a test problem, it is shown that the
inclusion of dynamic fluctuations may significantly change the vibrational
energy relaxation. In particular, it is found that relaxation occurs in two
phases, because for short times ( 200 fs) the spectral density
appears continuous due to the frequency-time uncertainty relation, while at
longer times the discrete nature of the bath becomes apparent. Considering the
excellent agreement between theory and experiment, it is speculated if this
behavior can explain the experimentally obtained biphasic relaxation the amide
I mode of N-methylacetamide.Comment: 24 pages, 7 figures, submitted to J. Chem. Phy
What is the orientation of the tip in a scanning tunneling microscope?
We introduce a statistical correlation analysis method to obtain information
on the local geometry and orientation of the tip used in scanning tunneling
microscopy (STM) experiments based on large scale simulations. The key quantity
is the relative brightness correlation of constant-current topographs between
experimental and simulated data. This correlation can be analyzed statistically
for a large number of modeled tip orientations and geometries. Assuming a
stable tip during the STM scans and based on the correlation distribution, it
is possible to determine the tip orientations that are most likely present in
an STM experiment, and exclude other orientations. This is especially important
for substrates such as highly oriented pyrolytic graphite (HOPG) since its STM
contrast is strongly tip dependent, which makes interpretation and comparison
of STM images very challenging. We illustrate the applicability of our method
considering the HOPG surface in combination with tungsten tip models of two
different apex geometries and 18144 different orientations. We calculate
constant-current profiles along the direction of the HOPG(0001)
surface in the V bias voltage range, and compare them with
experimental data. We find that a blunt tip model provides better correlation
with the experiment for a wider range of tip orientations and bias voltages
than a sharp tip model. Such a combination of experiments and large scale
simulations opens up the way for obtaining more detailed information on the
structure of the tip apex and more reliable interpretation of STM data in the
view of local tip geometry effects.Comment: Progress in Surface Science, accepted for publication, 25 pages
manuscript, 9 figures, abstract shortene
Predicting the accuracy of protein-ligand docking on homology models
Ligand-protein docking is increasingly used in Drug Discovery. The initial limitations imposed by a reduced availability of target protein structures have been overcome by the use of theoretical models, especially those derived by homology modeling techniques. While this greatly extended the use of docking simulations, it also introduced the need for general and robust criteria to estimate the reliability of docking results given the model quality. To this end, a large-scale experiment was performed on a diverse set including experimental structures and homology models for a group of representative ligand-protein complexes. A wide spectrum of model quality was sampled using templates at different evolutionary distances and different strategies for target-template alignment and modeling. The obtained models were scored by a selection of the most used model quality indices. The binding geometries were generated using AutoDock, one of the most common docking programs. An important result of this study is that indeed quantitative and robust correlations exist between the accuracy of docking results and the model quality, especially in the binding site. Moreover, state-of-the-art indices for model quality assessment are already an effective tool for an a priori prediction of the accuracy of docking experiments in the context of groups of proteins with conserved structural characteristics.Contract/grant sponsor: National Institutes of Health; contract/grant numbers: ES00768
Efficient model chemistries for peptides. I. Split-valence Gaussian basis sets and the heterolevel approximation in RHF and MP2
We present an exhaustive study of more than 250 ab initio potential energy
surfaces (PESs) of the model dipeptide HCO-L-Ala-NH2. The model chemistries
(MCs) used are constructed as homo- and heterolevels involving possibly
different RHF and MP2 calculations for the geometry and the energy. The basis
sets used belong to a sample of 39 selected representants from Pople's
split-valence families, ranging from the small 3-21G to the large
6-311++G(2df,2pd). The reference PES to which the rest are compared is the
MP2/6-311++G(2df,2pd) homolevel, which, as far as we are aware, is the more
accurate PES of a dipeptide in the literature. The aim of the study presented
is twofold: On the one hand, the evaluation of the influence of polarization
and diffuse functions in the basis set, distinguishing between those placed at
1st-row atoms and those placed at hydrogens, as well as the effect of different
contraction and valence splitting schemes. On the other hand, the investigation
of the heterolevel assumption, which is defined here to be that which states
that heterolevel MCs are more efficient than homolevel MCs. The heterolevel
approximation is very commonly used in the literature, but it is seldom
checked. As far as we know, the only tests for peptides or related systems,
have been performed using a small number of conformers, and this is the first
time that this potentially very economical approximation is tested in full
PESs. In order to achieve these goals, all data sets have been compared and
analyzed in a way which captures the nearness concept in the space of MCs.Comment: 54 pages, 16 figures, LaTeX, AMSTeX, Submitted to J. Comp. Che
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