共查询到20条相似文献,搜索用时 31 毫秒
1.
Following our recent studies of the thermodynamic properties of azaspiropentane and borospiropentane, in consideration of
their usefulness as new potential high energy materials, we follow up with ab initio calculations on the thermodynamic properties
of azaborospiropentanes. Properties reported in this study include optimized structural parameters, vibrational frequencies,
enthalpies of formation, specific enthalpies of combustion, proton affinities, and hydride affinities. Our results indicate
that azatriborospiropentane gives off most energy when combusted, as evidenced by its specific enthalpy of combustion of about
−52 kJ per gram.
Figure Optimized geometry for R-azatriborospiropentane (10)
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
2.
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
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.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
12.
Aminophosphine oxides and aminophosphonates are, in general, very stable compounds. However, following phosphorus–carbon bond
cleavage in aqueous acidic media these compounds sometimes decompose to phosphonic acids derivatives (PIII). Despite some controversy in the literature, careful analysis supported by theoretical studies leads to the conclusion that
decomposition to PIII derivatives proceeds via an elimination reaction.
Figure The decomposition of α-aminophosphine oxides to phosphonic acid derivatives (PIII) 相似文献
13.
Modelling of conformational changes in biopolymers is one of the greatest challenges of molecular biophysics. Metadynamics
is a recently introduced free energy modelling technique that enhances sampling of configurational (e.g. conformational) space
within a molecular dynamics simulation. This enhancement is achieved by the addition of a history-dependent bias potential,
which drives the system from previously visited regions. Discontinuous metadynamics in the space of essential dynamics eigenvectors
(collective motions) has been proposed and tested in conformational change modelling. Here, we present an implementation of
two continuous formulations of metadynamics in the essential subspace. The method was performed in a modified version of the
molecular dynamics package GROMACS. These implementations were tested on conformational changes in cyclohexane, alanine dipeptide
(terminally blocked alanine, Ace-Ala-Nme) and SH3 domain. The results illustrate that metadynamics in the space of essential
coordinates can accurately model free energy surfaces associated with conformational changes.
Figure The conformational free energy surface of cyclohexane in the space of the two most intensive collective motions.
相似文献
相似文献
14.
Based upon our preceding studies of the hydration of CO2, COS and CS2, accelerated by the carbonic anhydrase (CA) using simplified [ZnL3OH]+ complexes as model catalysts, we calculated the hydration mechanisms of both the uncatalyzed and the [ZnL3OH]+-catalyzed reactions (L = NH3) of isothiocyanates RNCS on the B3LYP/6-311+G(d,p) level of theory. Interestingly, the transition state for the favored metal
mediated reaction with the lowest Gibbs free energy is only slightly higher than in the case of CO2 (depending on the attacking atom (N or S). Calculations under inclusion of solvent corrections show a reduction of the selectivity
and a slight decrease of the Gibbs free energy in the rate-determining steps. The most plausible pathway prefers the mechanism
via a Lindskog proton-shift transition state leading to the thermodynamically most stable product, the carbamatic-S-acid.
Furthermore, powerful electron withdrawing substituents R of the cumulenic substrates influence the selectivity of the reaction
to a significant extent. Especially the CF3-group in trifluoromethylisothiocyanate reverses the selectivity. This investigation demonstrates that reaction principles
developed by nature can be translated to develop efficient catalytic methods, in this case presumably for the transformation
of a wide variety of heterocumulenes aside from CO2, COS and CS2.
Figure Competing transition structures for the [ZnL3OH]+-mediated activation of isothiocyanates
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
15.
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
16.
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
17.
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
18.
Computational models for the shuttling motion of the macrocycle in rotaxane-based molecular switches
The shuttling motion of a macrocycle in rotaxane-based molecular switching devices has been studied by computational density
functional methods. In the test case, energy profiles corresponding to the dethreading process of different types of guest
molecules in a cyclobis(paraquat-p-phenylene) host verified the experimental preference of the tetrathiafulvalene recognition
site over the dioxynaphthalene site in a Stoddart-Heath type molecular device. Furthermore, modification of the redox state
of either the macrocycle or the guest molecule resulted in considerable changes in the computational energy profiles, which
can be utilized in explaining the behavior of the host-guest system. In order to study the effect of chemical oxidation/reduction
in the guest molecule, we have investigated a prototypical shaft including two octahedral ruthenium complexes linked by a
conjugated C14 carbon chain, where the shuttling motion can be triggered by changing the electronic environment of the active complexes
with ligand exchange reactions. The computational results also indicated effective communication between the macrocycle and
the conjugated carbon chain, therefore showing the importance of non-covalent host-guest interactions in the control of the
motion.
Figure A computational model for a chemically controlled molecular switch 相似文献
19.
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
20.
Athanassios Stavrakoudis 《Journal of molecular modeling》2009,15(2):165-171
In a recent study C8γ (complement protein) with Cys40Ala substitution and a C8α derived peptide with Cys164Ala substitution
were co-crystallized and their binding mode was revealed. Computer modeling and molecular dynamics simulations were performed
in order to check the hypothesis that the residues Ala164 of C8α and Ala40 of C8γ occupied the right position if cysteine
residues were in their place for disulfide bonding. Substitution of these two alanine residues with cysteine along with disulfide
bond creation via molecular modeling and subsequent molecular dynamics simulation of the complex corroborated the hypothesis,
which was also confirmed from recent crystallographic data. Average RMSD between backbone atoms of the indel peptide during
the MD trajectory in comparison with the corresponding sequence of crystal structure of the C8α/γ complex was found only 0.085
nm.
Figure Modeling the C*y/α comlexation. Ribbon representation of the C8y complexed with C8α indel peptide initial (green/cyan) X-ray
structure and the final MD conformation (magenta/orange) after imposing the disulfide link. Average RMSD between backbone
atoms of the indel peptide during MD trajectory in comparison with the corresponding sequence of crystal structure of the
C8α/y complex was found only 0.085nm.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献