共查询到20条相似文献,搜索用时 78 毫秒
1.
Following our recent study on triazane, we present a follow-up study on the thermodynamic properties of triazane’s unsaturated
analog, triazene. We predict optimized structural parameters, vibrational frequencies, enthalpies of formation, enthalpies
of combustion, specific enthalpies of combustion, and proton affinities. Our results indicate that the cis form of triazene
has a specific enthalpy of combustion of −15.2 kJ g−1 and the trans form has a specific enthalpy of combustion of −14.7 kJ g−1.
Figure Structures of cis- and trans-triazane, N3H3 相似文献
2.
As a follow-up study to our study on tetrazane (N4H6), we present computed thermodynamic properties of triazane (N3H5). Calculated properties include optimized geometries, infrared vibrations, enthalpy of formation, enthalpy of combustion,
and proton affinities. We have also mapped the potential energy surface as the molecule is rotated about the N-N bond. We
have predicted a specific enthalpy of combustion for triazane of about -20 kJ g−1.
Figure Schematic diagram of the dielectric barrier discharge (left) and typical temporal profiles of voltage and current, as obtained
from the simulations (right) 相似文献
3.
A 3D QSAR analysis has been performed on a series of 67 benzodiazepine analogues reported as γ-secretase inhibitors using
molecular field analysis (MFA), with G/PLS to predict steric and electrostatic molecular field interaction for the activity.
The MFA study was carried out using a training set of 54 compounds. The predictive ability of model developed was assessed
using a test set of 13 compounds ( as high as 0.729). The analyzed MFA model has demonstrated a good fit, having r2 value of 0.858 and cross validated coefficient, value as 0.790. The analysis of the best MFA model provided insight into possible modification of the molecules for better
activity.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
4.
Stewart JJ 《Journal of molecular modeling》2008,14(6):499-535
The applicability of the recently developed PM6 method for modeling various properties of a wide range of organic and inorganic
crystalline solids has been investigated. Although the geometries of most systems examined were reproduced with good accuracy,
severe errors were found in the predicted structures of a small number of solids. The origin of these errors was investigated,
and a strategy for improving the method proposed.
Figure Detail of Structure of Dihydrogen Phosphate in KH2PO4 (upper pair) and in (CH3)4NH2PO4. (Footnote): X-ray structures on left, PM6 structure on right.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
5.
Inhibition of leukocyte-specific protein tyrosine kinase (Lck) activity offers one of the approaches for the treatment of
T-cell mediated inflammatory disorders including rheumatoid arthritis, transplant rejection and inflammatory bowel disease.
To explore the relationship between the structures of the N-4 Pyrimidinyl-1H-indazol-4-amines and their Lck inhibition, 3D-QSAR
study using CoMFA analysis have been performed on a dataset of 42 molecules. The bioactive conformation of the template molecule,
selected as the most potent molecule 23 from the series was obtained by performing molecular docking at the ATP binding site of Lck, which is then used to build
the rest of the molecules in the series. The constructed CoMFA model is robust with of 0.603 and conventional r2 of 0.983. The predictive power of the developed model was obtained using a test set of 10 molecules, giving predictive correlation
coefficient of 0.921. CoMFA contour analysis was performed to obtain useful information about the structural requirements
for the Lck inhibitors which could be utilized in its future design.
Figure CoMFA steric contour map. Sterically favored areas (contribution level 80%) are represented by green polyhedra. Sterically
disfavored areas (contribution level 20%) are represented by yellow polyhedra. The active molecule 23 shown in capped sticks.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
6.
The ONIOM2 (B3LYP/6–31G (d, p): PM3) and B3LYP/6–31G (d, p) methods were applied to investigate the interaction between STI-571 and abelson tyrosine kinase binding site. The complex of N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)- phenyl]-benzamide (part of STI-571) and related 16 amino acid residues were found at B3LYP/6–31G (d, p) level to have hydrogen bonds and π....π stacking interaction,
their binding energy via HAF optimization was −20.4 kcal mol−1. The results derived from this study agreed well with the reported observation.
Figure Optimized structure of STI-571 and Thr315 in abelson tyrosine kinase based on ONIOM2 method 相似文献
7.
Vuk Micovic Milovan D. Ivanovic Ljiljana Dosen-Micovic 《Journal of molecular modeling》2009,15(3):267-280
An automated docking procedure was used to study binding of a series of δ-selective ligands to three models of the δ-opioid
receptor. These models are thought to represent the three ligand-specific receptor conformations. Docking results are in agreement
with point mutation studies and suggest that different ligands—agonists and antagonists—may bind to the same binding site
under different receptor conformations. Docking to different receptor models (conformations) also suggests that by changing
to a receptor-specific conformation, the receptor may open or close different binding sites to other ligands.
Figure Ligands 5 (green) and 6 (orange) in bindingpocket BP1 of the R1 δ-opioid receptor model 相似文献
8.
Grochala W 《Journal of molecular modeling》2008,14(10):887-890
We have analyzed the electronic structure and chemical bonding for molecular adducts of the Ag(II)F2 molecule with various aza Lewis bases including ammonia, nitriles, secondary amines, and their derivatives exhibiting various
degrees of fluorination. Density functional theory calculations indicate that a progressive shift occurs of the spin density
from the Ag center towards the coordinating nitrogen atoms of aza ligands, as the ligation energy increases. Chemistry of
Ag(II) might be extended with little effort beyond the known aza connections, to include nitriles, perfluorinated nitriles
and perfluorinated amines.
Figure Properties of a variety of novel adducts of the AgF2 molecule with two aza bases (L), possible precursors of the AgF2L2 extended solids, were assessed by the DFT calculations
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
This work is dedicated to memory of Wojciech Ochmański, unforgettable person, good-hearted man, whose craftsmanship in work
was second-to-none. 相似文献
9.
William N. Setzer 《Journal of molecular modeling》2009,15(2):197-201
Quantum chemical calculations at the B3LYP/6-31G* level of theory have been carried out on 20 celastroid triterpenoids to
obtain a set of molecular electronic properties and to correlate these with cytotoxic activities. The cytotoxic activities
of these compounds can be roughly correlated with electronic effects related to nucleophilic addition to C(6) of the compounds:
The energies of the frontier molecular orbitals (E
HOMO and E
LUMO), the HOMO-LUMO energy gap, the dipole moment, the charge on C(6), and the electrophilicity on C(6).
Figure LUMO of Pristimerin. 相似文献
10.
Twelve binary and eight ternary supersystems between thymine and methanol, and water were investigated in the ground state
at the B3LYP and MP2 levels of theory using B3LYP/6-311 + + G(d,p) basis functions. The thermodynamics of complex formations
and the mechanisms of intermolecular proton transfers were clarified in order to find out the most stable H-boned system.
It was established that the energy barriers of the water/methanol-assisted proton transfers are several times lower than those
of the intramolecular proton transfers in the DNA/RNA bases. The X-ray powder spectra of thymine, and this precrystallized
from water and methanol showed that water molecules are incorporated in the crystal lattice of thymine forming H-bridges between
thymine molecules.
Figure Intermolecular H-bonding of thymine 相似文献
11.
Coro J Alvarez-Puebla R Montero AL Suárez M Martin N Perez-Pineiro R 《Journal of molecular modeling》2008,14(7):641-647
Based on experimental evidence and DFT studies, a probable cyclization route to 1,3,5-thiadiazinanes-2-thiones in aqueous
medium is proposed. Experimental facts suggest the formation of a {[hydroxymethyl (substituted) carbamothioyl] sulfanyl}methanol
intermediate via reaction of dithiocarbamate (DTC) and formaldehyde. Nucleophilic addition of glycine to this intermediate
generates an adduct that undergoes intramolecular heterocyclization via an SN2 reaction. Computational calculations predict an active role of water in the reaction mechanism that promotes intramolecular
cyclization.
Figure Energy profile of the proposed reaction mechanism for the synthesis of thiadiazinane-2-thione ring 11 in aqueous medium from
a (hydroxymethylcarbamothioyl)sulfanylmethanol intermediate, 9 相似文献
12.
Jarosław J. Panek Thomas R. Ward Aneta Jezierska Marjana Novič 《Journal of molecular modeling》2009,15(3):257-266
Due to its highly specific and very strong binding, the (strept)avidin–biotin system forms the basis for numerous applications
in the life sciences: immunoassays, DNA detection systems, affinity chromatography, etc. Fine-tuning of the ligand binding
abilities of this system might provide new technologies with relevance to nanoscale research. Here, we report our computational
investigations on wild type (WT) and modified streptavidin (SAV), assessing the impact of fluorination of tryptophan residues
on biotin binding ability. Complexes of biotin with four SAV protein variants (WT-SAV, 4fW-SAV, 5fW-SAV and 6fW-SAV) were
studied. We found that protein stability and folding are predicted to be weakly affected by fluorination. The host protein
binding pocket decreases its ability to form numerous hydrogen bonds to biotin in the case of the 4fW-SAV variant. Conversely,
the 5fW-SAV mutant is predicted to have an even more stable ligand–host hydrogen bonding network than WT-SAV. Thermodynamic
perturbation investigations predict a decrease in biotin binding free energy from 3.0 to 6.5 kcal/mol per tetrameric host,
with the 5fW-SAV mutant being least affected. Overall, the computational findings indicate that 6fW-SAV and, especially, 5fW-SAV
to be promising variants of streptavidin for potential modifiable picomolar binding of the biotin ligand family.
Figure Hydrogen bonding framework of the biotin–streptavidin system
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
13.
The possibility that stable complexes may be formed between alpha particles (He2+) and small molecules is investigated using QCISD quantum mechanical calculations. Implications for their presence in the
terrestrial atmosphere and/or in interstellar space are discussed.
Figure Optimized structure of a stable H2OHe2+ complex 相似文献
14.
Hetero-Diels-Alder (HDA) reaction of methyl glyoxylate with buta-1,3-diene has been investigated using multireference methods
(complete active space SCF and multi-reference perturbation theory) and compared with several single-reference methods (including
DFT) often used in calculations of catalysed [4+2] cycloadditions. Concerted and stepwise mechanisms, found in the literature,
are compared. It is shown, that the stepwise mechanism may be a result of choosing unbalanced active space. Such choice leads
to very close singlet and triplet states in the intermediate geometry - an artificial effect, that disappears if properly
balanced active space is used (here, we use active space of 12 orbitals and 12 electrons). Conclusions concerning the mechanism
and usefulness of the applied methodology are drawn, which might be important for theoretical investigation of stereoselectivity
and specificity of catalysts for the HDA reaction.
Figure Hetero-Diels-Alder reaction of alkyl glyoxylates with buta-1,3-diene, investigated using multi- and single-reference ab initio
methods
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
15.
Quantum chemical (Hartree-Fock) calculations were performed on neutral and protonated saxitoxin in order to obtain optimum
geometries, rotational energy barriers for the guanidinium ions and proton affinities. For comparison purposes, as model compounds,
guanidinium systems in five and six membered rings were also investigated. In addition, DFT (B3LYP) calculations with the
6-31G** basis set were performed and the sodium affinities of the guanidinium groups in saxitoxin were obtained. It was concluded
that the inhibition of the sodium channels by the saxitoxin is due to the interaction of the guanidinium group with carboxylate
groups from the wall of the channel and not to the binding of the sodium ions.
Figure Calculated structure of Compound 1, neutral saxitoxin.
a Calculated structure of Compound 1a, saxitoxin protonated on the guanidine of the five-membered ring.
b Calculated structure of Compound 1b, saxitoxin protonated on the guanidine of the six-membered ring 相似文献
16.
This work presents new developments of the moving-domain QM/MM (MoD-QM/MM) method for modeling protein electrostatic potentials.
The underlying goal of the method is to map the electronic density of a specific protein configuration into a point-charge
distribution. Important modifications of the general strategy of the MoD-QM/MM method involve new partitioning and fitting
schemes and the incorporation of dynamic effects via a single-step free energy perturbation approach (FEP). Selection of moderately
sized QM domains partitioned between and C (from C=O), with incorporation of delocalization of electrons over neighboring domains, results in a marked improvement
of the calculated molecular electrostatic potential (MEP). More importantly, we show that the evaluation of the electrostatic
potential can be carried out on a dynamic framework by evaluating the free energy difference between a non-polarized MEP and
a polarized MEP. A simplified form of the potassium ion channel protein Gramicidin-A from Bacillus brevis is used as the model system for the calculation of MEP.
Figure Schematic representation of the Moving Domain QM/MM method 相似文献
17.
Oliver Mirus Tihana Bionda Arndt von Haeseler Enrico Schleiff 《Journal of molecular modeling》2009,15(8):971-982
Transport of polypeptides across membranes is a general and essential cellular process utilised by molecular machines. At
least one component of these complexes contains a domain composed of three tetratricopeptide repeat (3-TPR) motifs. We have
focussed on the receptor Toc64 to elucidate the evolved functional specifications of its 3-TPR domain. Toc64 is a component
of the Toc core complex and functionally replaces Tom70 at the outer membrane of mitochondria in plants. Its 3-TPR domain
recognises the conserved C-terminus of precursor-bound chaperones. We built homology models of the 3-TPR domain of chloroplastic
Toc64 from different species and of the mitochondrial isoform from Arabidopsis. Guided by modelling, we identified residues essential for functional discrimination of the differently located isoforms
to be located almost exclusively on the convex surface of the 3-TPR domain. The only exception is at568Ser/ps557Met, which is positioned in the ligand-binding groove. The functional implications of the homology models are discussed.
Figure Motion contained within the 2nd eigenvector of the Calpha covariance matrix of the 3-TPR domain of atToc64-V indicated by
a porcupine plot
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
18.
Ankyrin repeat proteins (ARPs) appear to be abundant in organisms from all phyla, and play critical regulatory roles, mediating
specific interactions with target biomolecules and thus ordering the sequence of events in diverse cellular processes. ARPs
possess a non-globular scaffold consisting of repeating motifs named ankyrin (ANK) repeats, which stack on each other. The
modular architecture of ARPs provides a new paradigm for understanding protein stability and folding mechanisms. In the present
study, the stability of various C-terminal fragments of the ARP p18INK4c was investigated by all-atomic 450 ns molecular dynamics (MD) simulations in explicit water solvent. Only motifs with at
least two ANK repeats made stable systems in the available timescale. All smaller fragments were unstable, readily losing
their native fold and α-helical content. Since each non-terminal ANK repeat has two hydrophobic sides, we may hypothesize
that at least one hydrophobic side must be fully covered and shielded from the water as a necessary, but not sufficient, condition
to maintain ANK repeat stability. Consequently, at least two ANK repeats are required to make a stable ARP.
Figure Structure of the p18INK4c protein (PDB entry 1IHB, chain B), which is a member of the cyclin-dependent kinase inhibitor (INK)
tumor suppressor family with five ankyrin (ANK) repeat modules. The figure was generated by PyMol
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
19.
Salcedo R 《Journal of molecular modeling》2007,13(9):1027-1031
A global electrophilicity parameter and the aromaticity of some heterocyclic polyaromatic hydrocarbons were evaluated on the
basis of DFT calculations. The substitution of carbon atoms by nitrogen atoms dramatically changes the global electrophilicity
of the molecules, with the fully substituted molecule being the most electrophilic with a reactivity very close to that of
fullerene.
Figure Fully substituted heterohexabenzocoronene
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
20.
Pharmacophore mapping studies were undertaken for a series of molecules belonging to pyrrolopyrimidines, indolopyrimidines
and their congeners as multidrug resistance-associated protein (MRP1) modulators. A five-point pharmacophore with two hydrogen
bond acceptors (A), one lipophilic/hydrophobic group (H), one positive ionic feature (P) and one aromatic ring (R) as pharmacophoric
features was developed. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation
coefficient of r
2 = 0.799 for training set molecules. The model generated showed excellent predictive power, with a correlation coefficient Q
2 = 0.679 for an external test set of 20 molecules. The pharmacophore was further validated using four structurally diverse
compounds with MRP1 modulatory activity. These compounds mapped well onto four of the five features of the pharmacophore.
The pharmacophore proposed here was then utilised for the successful retrieval of active molecules with diverse chemotypes
from database search. The geometry and features of pharmacophore are expected to be useful for the design of selective MRP1
inhibitors.
Figure Alignment of multidrug resistance-associated protein (MRP1) inhibitors with the developed pharmacophore.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献