A computational study of hydrogen-bonded complexes between the oxo-/hydroxo-amino N7/9H tautomers of guanine and water, methanol,
and hydrogen peroxide has been performed at the B3LYP/6-31+G(d) level of theory. The mechanisms of the water-, methanol-,
and hydrogen peroxide-assisted proton transfers in guanine were studied and compared with the intramolecular proton transfer
in guanine in the gas phase. It was found that the assisted proton transfers pass through about three times lower energy barriers
than those found for isolated guanine tautomers.
Figure DFT study of the gas phase proton transfer in guanine assisted by water, methanol and hydrogen peroxide 相似文献
Twelve H-bonded supersystems constructed between the adenine tautomers and methanol, ethanol, and i-propanol were studied
at the B3LYP and MP2 levels of theory using 6-311G(d,p) and 6-311++G(d,p) basis functions. The thermodynamic parameters of
the complex formations were calculated in order to estimate the exact stability of the supersystems. It was proven that the
calculated energy barriers of the alcohol-assisted proton transfers are about 60% lower than those of the intramolecular proton
transfers in adenine found earlier (Gu and Leszczynski in J Phys Chem A 103:2744–2750, 1999).
Figure H-bonded complex between i-propanol and adenine 相似文献
Full geometric optimization of endo,endo-tetracyclo[4.2.1.13,6.02,7]dodeca-4,9-diene (TTDD) has been carried out by ab initio and DFT/B3LYP methods and the structure of the molecule investigated. The double bonds of TTDD molecule are endo pyramidalized. The structure of π-orbitals and their mutual interactions for TTDD molecule were investigated. The cationic
intermediates and products obtained as a result of the addition reaction have been studied using the HF/6-311G(d), HF/6-311G(d,p)
and B3LYP/6-311G(d) methods. The bridged bromonium cation isomerized into the more stable N- and U-type cations and the difference
between the stability of these cations is small. The N- and U-type reaction products are obtained as a result of the reaction,
which takes place via the cations in question. The stability of exo, exo and exo, endo isomers of N-type product are nearly the same and the formation of both isomers is feasible. The U-type product basically
formed from the exo, exo-isomer. Although the U-type cation was 0.68 kcal mol−1 more stable than the N-type cation, the U-type product was 4.79 kcal mol−1 less stable than the N-type product.
Figure The energy diagram of TTDD–Br2 system (kcal mol−1)(MP2/6-311G*//HF/6-311G*) 相似文献
The reaction mechanism of acetylcholine hydrolysis by acetylcholinesterase, including both acylation and deacylation stages
from the enzyme-substrate (ES) to the enzyme-product (EP) molecular complexes, is examined by using an ab initio type quantum mechanical – molecular mechanical (QM/MM) approach. The density functional theory PBE0/aug-6–31+G* method for
a fairly large quantum part trapped inside the native protein environment, and the AMBER force field parameters in the molecular
mechanical part are employed in computations. All reaction steps, including the formation of the first tetrahedral intermediate
(TI1), the acylenzyme (EA) complex, the second tetrahedral intermediate (TI2), and the EP complex, are modeled at the same
theoretical level. In agreement with the experimental rate constants, the estimated activation energy barrier of the deacylation
stage is slightly higher than that for the acylation phase. The critical role of the non-triad Glu202 amino acid residue in
orienting lytic water molecule and in stabilizing the second tetrahedral intermediate at the deacylation stage of the enzymatic
process is demonstrated.
Figure The computed energy diagram for the reaction path from the enzyme – substrate complex (ES) to the enzyme-product complex (EP). 相似文献
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
The recently introduced multipole approach for computing the molecular electrostatic potential (MEP) within the semiempirical
neglect of diatomic differential overlap (NDDO) framework [Horn AHC, Lin Jr-H., Clark T (2005) Theor Chem Acc 114:159–168] has been used to obtain atomic charges of nearly ab initio quality by scaling the semiempirical
MEP. The parameterization set comprised a total of 797 compounds and included not only the newly parameterized AM1* elements
Al, Si, P, S, Cl, Ti, Zr, and Mo but also the standard AM1 elements H, C, N, O and F. For comparison, the ZDO-approximated
MEP was also calculated analytically in the spd-basis. For the AM1*-optimized structures, single-point calculations at the B3LYP, HF and MP2 levels with the 6-31G(d) and
LanL2DZP basis sets were performed to obtain the MEP. The regression analysis of all 12 combinations of semiempirical and
ab initio MEP data yielded correlation coefficients of at least 0.99 in all cases. Scaling the analytical and multipole-derived
semiempirical MEP by the regression coefficients yielded mean unsigned errors below 2.6 and 1.9 kcal mol−1, respectively. Subsequently, for 22 drug molecules from the World Drug Index, atomic charges were computed according to the
RESP procedure using XX/6-31G(d) (XX=B3LYP, HF, MP2) and scaled AM1* multipole MEP; the correlation coefficients obtained
are 0.83, 0.85 and 0.83, respectively. Figure: Schematic representation of the atomic charge generation: The molecular electrostatic potential (MEP) is calculated using
the AM1* Hamiltonian; then the semiempirical MEP is scaled to DFT or ab initio level, and atomic charges are generated subsequently
by the restraint electrostatic potential (RESP) fit method.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorized users.
Proceedings of “Modeling Interactions in Biomolecules II”, Prague, September 5th–9th, 2005. 相似文献
The present study reports the geometries, electronic structures, growth behavior, and stabilities of neutral and ionized copper-doped germanium clusters containing 1–20 Ge atoms within the framework of linear combination of atomic orbitals density functional theory (DFT) under the spin-polarized generalized gradient approximation. It was found that Cu-capped Gen (or Cu-substituted Gen+1) and Cu-encapsulated Gen clusters mostly occur in the ground state at a particular cluster size (n). In order to explain the relative stabilities of the ground-state clusters, parameters such as the average binding energy per atom (BE), the embedding energy (EE), and the fragmentation energy (FE) of the clusters were calculated, and the resulting values are discussed. To explain the chemical stabilities of the clusters, parameters such as the energy gap between the highest occupied and the lowest unoccupied molecular orbitals (the HOMO–LUMO gap), the ionization energy (IP), the electron affinity (EA), the chemical potential (μ), the chemical hardness (η), and the polarizability were calculated, and the resulting values are also discussed. Natural atomic orbital (NAO) and natural bond orbital (NBO) analyses were also used to determine the electron-counting rule that should be applied to the most stable Ge10Cu cluster. Finally, the relevance of the calculated results to the design of Ge-based superatoms is discussed.
Figure Contributions of the valance orbitals of the Ge and Cu atom(s) to the HOMO of the ground-state icosahedral Ge10Cu cluster obtained from NBO analysis. The numbers below the clusters represent the occupancies of the HOMO orbitals
Members of the bacterial genus Sphingomonas are known to produce highly viscous polysaccharides in solution. The exopolysaccharide PS-EDIV was produced by Sphingomonas pituitosa strain DSM 13101, purified using centrifugation, and precipitation and its structure was elucidated by 1D and 2D NMR techniques
and chemical microderivatization combined with various mass spectrometric techniques. The following repeating unit of the
polysaccharide could be identified:
In addition, the polysaccharide also contains acetyl and glyceryl groups whose exact positions were not determined. PS-EDIV
is similar in structure to a known exopolysaccharide but differs in being the first bacterial polysaccharide in which two
different glucuronic acids are combined. It caused a high viscosity of the culture broth after cultivation for 48 h, although
a gelation was not observed. 相似文献
The alkali-extractable water-soluble polysaccharides F1SS isolated from the cell wall of two isolates of the pathogen Neotestudina rosatii and one of Pseudophaeotrichum sudanense, which is now considered as a synonym of the former, have been studied by methylation analysis, GC–MS and NMR spectroscopy.
The three polysaccharides differ mainly in their content in galactofuranose, and have the following idealized repeating unit:
相似文献
Ionization potential (IP), electron affinity (EA), dipole moment (μ) and electronic polarizability (α) of 1-, 3- and 6-nitrobenzo[a]pyrene isomers (1-NBaP, 3-NBaP, 6-NBaP) were determined by using density functional theory (DFT) and recent semiempirical PM6 methods. Calculated IP value remains
almost constant along the series of isomers, while EA value depends on the nitro group position, increasing by ca. 0.2 eV
on passing from 6- to 1-NBaP (or 3-NBaP) isomer. Stability, μ and α values decrease in the order 6-NBaP < 1-NBa ∼ 3-NBaP, the largest μ variation being predicted to be 1.5 D (30%) by DFT computations. The results obtained herein are consistent
with the observed greater mutagenic activity of 3- and 1-NBaP in comparison to 6-NBaP isomer, suggesting that both binding to enzyme, which depends on electric properties, and reduction process, which is related
to EA value may be crucial steps in the mutagenic mechanism of this series of isomers.
Figure Structure and dipole moment vector of nitrobenzo[a]pyrene isomers 相似文献
Ionic hydrocarbon compounds that contain hypercarbon atoms, which bond to five or more atoms, are important intermediates in chemical synthesis and may also find applications in hydrogen storage. Extensive investigations have identified hydrocarbon compounds that contain a five- or six-coordinated hypercarbon atom, such as the pentagonal-pyramidal hexamethylbenzene, C6(CH3)62+, in which a hexacoordinate carbon atom is involved. It remains challenging to search for further higher-coordinated carbon in ionic hydrocarbon compounds, such as seven- and eight-coordinated carbon. Here, we report ab initio density functional calculations that show a stable 3D hexagonal-pyramidal configuration of tropylium trication, (C7H7)3+, in which a heptacoordinate carbon atom is involved. We show that this tropylium trication is stable against deprotonation, dissociation, and structural deformation. In contrast, the pyramidal configurations of ionic C8H8 compounds, which would contain an octacoordinate carbon atom, are unstable. These results provide insights for developing new molecular structures containing hypercarbon atoms, which may have potential applications in chemical synthesis and in hydrogen storage.
Graphical abstract Possible structural transformations of stable configurations of (C7H7)3+, which may result in the formation of the pyramidal structure that involves a heptacoordinate hypercarbon atom.
Rv0045c is an esterase involved in lipid metabolism of Mycobacterium tuberculosis. It belongs to the α/β hydrolase family. In the current study, we performed sequence- and structure-based analysis of Rv0045c followed by molecular dynamics (MD) simulation for 100 ns to investigate conformational changes in the enzyme. Sequence analysis revealed that this enzyme is possibly a hormone-sensitive lipase. Further, through structural analysis, a putative catalytic tetrad containing “Ser-Asp-Ser-His” and residues involved in the formation of an oxyanion hole were identified. MD simulation of Rv0045c revealed a conformational transition from an open to a closed state. The active site pocket was found to be gated by four loops. The potential role of the cap domain and the mobile histidine is discussed. From the simulation, we see that the conformational changes mimic the different stages in the reaction mechanism of Rv0045c. These results support the hypothesis that free enzyme simulation encompasses all the conformations necessary for the different stages of catalysis. Our findings add to the growing knowledge of an important family of esterases in Mycobacterium tuberculosis.
Synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. The synthetic strategy involves sequential glycosylation of suitably protected monosaccharide intermediates under similar glycosylation reaction conditions. Thioglycosides have been used as glycosyl donor throughout the synthetic strategy. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique.
Graphical abstract Facile synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique.
Small heat shock proteins (sHSPs) are heat shock proteins sized 12–43 kDa that can protect proteins from denaturation, particularly under high temperature; sHSPs thus increase the heat tolerance capability of an organisms enabling survival in adverse climates. sHSP20 is overexpressed in Oenococcus oeni in response to low temperatures. However, we found that overexpression of sHSP20 in Escherichia coli BL21 increased the microbial survival ratio at 50 °C by almost 2 h. Adding sHSP20 to the glutamate dehydrogenase solution significantly increased the stability of the enzyme at high temperature (especially at 60–70 °C), low pH values (especially below 6.0), and high concentration of metal ions of Ga2+, Zn2+, Mn2+, and Fe3+. Notably, the coexpression of sHSP20 significantly enhanced soluble expression of laccase from Phomopsis sp. XP-8 (CCTCCM209291) in E. coli without codon optimization, as well as the activity and heat stability of the expressed enzyme. In addition to the chaperone activity of sHSP20 in the gene containing host in vivo and the enzyme heat stability in vitro, our study indicated the capability of coexpression of sHSP20 to increase the efficiency of prokaryotic expression of fungal genes and the activity of expressed enzymes.
Hyaluronan lyase from Streptococcus pneumoniae can degrade hyaluronic acid, which is one of the major components in the extracellular matrix. Hyaluronan can regulate water balance, osmotic pressure, and act as an ion exchange resin. Followed by our recent work on the catalytic reaction mechanism and substrate binding mode, we in this work further investigate the functional role of active site arginine residue, R462, in the degradation of hyaluronan. The site directed mutagenesis simulation of R462A and R462Q were modeled using a combined quantum mechanical and molecular mechanical method. The overall substrate binding features upon mutations do not have significant changes. The energetic profiles for the reaction processes are essentially the same as that in wild type enzyme, but significant activation barrier height changes can be observed. Both mutants were shown to accelerate the overall enzymatic activity, e.g., R462A can reduce the barrier height by about 2.8 kcal mol–1, while R462Q reduces the activation energy by about 2.9 kcal mol–1. Consistent with the active site model calculated using density functional theory, our results can support that the positive charge on R462 guanidino side chain group plays a negative role in the catalysis. Finally, the functional role of R462 was proposed to facilitate the formation of initial enzyme-substrate complex, but not in the subsequent catalytic degradation reaction.
The lipopolysaccharide (LPS) of Escherichia coli M-17 was isolated, studied, chemically identified, and shown to be an apyrogenic compound of low toxicity. Investigation of the effect of this LPS on T- and B-lymphocytes suggests that it can be used as a mitogen in blast transformation reactions, as it is only slightly less active than the commercial preparation. Double immunodiffusion in agar by Ouchterlony revealed that the LPS of E. coli M-17 in a homologous system exhibited an antigenic activity and did not interact with the antisera against representatives of other Enterobacteriaceae species (Budvicia aquatica, Rahnella aquatilis, and Pragia fontium) in serological cross-reactions. Mild acid hydrolysis yielded the following structural components of the lipopolysaccharide molecule: lipid A, core oligosaccharide, and O-specific polysaccharide. The structure of the O-specific polysaccharide determined using the data on the monosaccharide composition and the 1H and 13NMR spectra was found to be typical of representatives of the E. coli serogroup O2: 相似文献
Src tyrosine kinases are a family of non-receptor proteins that are responsible for the growth process, cellular proliferation, differentiation and survival. Lack of Src kinase control has been associated with the development of certain human cancers. This family of proteins is constituted of four domains, with SH1 being the kinase or catalytic domain. SH1 also presents three important regulatory sites. Two residues, Tyr416 and Tyr527, are responsible for important phosphorylation processes that lead to, respectively, activation and deactivation of these kinases. More recently, however, a set of four cysteine residues located near the C-terminus-Cys483, Cys487, Cys496 and Cys498-has been associated with the activation of the Src kinases through S-nitrosylation reactions. Particularly, the Cys498 has been specified as a fundamental residue when considering this regulatory mechanism. Aiming to understand the role of these four cysteines in S-nitrosylation, theoretical studies of electrostatic, steric and hydrophobic properties were performed with a sequence of 20 amino acids, enclosing the four cysteine residues under study, extracted from the PDB coordinates of the crystal obtained from the inactive state of Src kinase. Results indicate that Cys498 is buried deeply in the protein, in hydrophobic surroundings in which NO is more likely to suffer decomposition into the electrophilic intermediates known to be responsible for S-nitrosylation reactions. Electronic calculated properties, such as punctual atomic charges, electrostatic potentials and molecular orbital energy, also demonstrated the good nucleophilic potential of Cys498.
Graphical Abstract Structure of Src kinase with zoomed area representing the 20 amino acids comprising the CC motif extracted from the whole protein structure. Right upper panel Electrostatic potential map, right lower panel hydrophilic map in anterior view
Phospholipase A2 (PLA2) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA2 is considered to be one of the efficient methods to control inflammation. In silico docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA2 (ppsPLA2) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies. In silico analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA2 (hnpsPLA2) was determined using molecular docking studies. In order to corroborate the in silico results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA2. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.
