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1.
The intermolecular interaction energies in central guanine triad of telomeric B-DNA were estimated based on ab initio quantum
chemistry calculations on the MP2/aDZ level of theory. The source of structural information was molecular dynamics simulation
of both canonical (AGGGTT) and oxidized (AG8oxoGGTT) telomere units. Our calculations demonstrate that significant stiffness
of central triad occurs if 8oxoG is present. The origin of such feature is mainly due to the increase of stacking interactions
of 8oxoG with neighbouring guanine molecules and stronger hydrogen bonding formation of 8oxoG with cytosine if compared with
canonical guanine. Another interesting observation is the context independence of stacking interactions of 8oxoG. Unlike to
5′-G2/G3-3′ and 5′-G3/G4-3′ sequences which are energetically different, 5′-G2/8oxoG3-3′ and 5′-8oxoG3/G4-3′ sequences are almost iso-energetic. 相似文献
2.
We performed three 3-ns molecular dynamics simulations of d(CGCGAATTCGCG)2 using the AMBER 8 package to determine the effect of salt concentration on DNA conformational transitions. All the simulations
were started with A-DNA, with different salt concentrations, and converged with B-DNA with similar conformational parameters.
However, the dynamic processes of the three MD simulations were very different. We found that the conformation transition
was slow in the solution with higher salt concentration. To determine the cause of this retardation, we performed three additional
1.5-ns simulations starting with B-DNA and with the salt concentrations corresponding to the simulations mentioned above.
However, astonishingly, there was no delayed conformation evolution found in any of the three simulations. Thus, our simulation
conclusion is that higher salt concentrations slows the A → B conformation transition, but have no effect on the final stable
structure.
Figure A-DNA and B-DNA. (a) is the canonical A-DNA, and (b) is the canonical B-DNA. Looking from the central major groove 相似文献
3.
A frequent task in computer-aided drug design is to identify novel chemotypes similar in activity but structurally different
to a given reference structure. Here we report the development of a novel method for atom-independent similarity comparison
of molecular fragments (substructures of drug-like molecules). The fragments are characterized by their local surface properties
coded in the form of 3D pharmacophores. As surface properties, we used the electrostatic potential (MEP), the local ionization
energy (IEL), local electron affinity (EAL) and local polarizability (POL) calculated on isodensity surfaces. A molecular fragment can then be represented by a minimal
set of extremes for each surface property. We defined a tolerance sphere for each of these extremes, thus allowing us to assess
the similarity of fragments in an analogous manner to classical pharmacophore comparison. As a first application of this method
we focused on comparing rigid fragments suitable for scaffold hopping. A retrospective analysis of successful scaffold hopping
reported for Factor Xa inhibitors [Wood MR et al (2006) J Med Chem 49:1231] showed that our method performs well where atom-based
similarity metrics fail.
Figure Encoding surface hotspots as a ParaFrag pharmacophore 相似文献
4.
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
5.
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
6.
Kaustubh A. Joshi Dinannath D. Patil Shridhar P. Gejji 《Journal of molecular modeling》2009,15(4):383-390
Hydroxyquinolone derivatives have proven to be useful for inhibition at the glycine binding site of N-methyl-D-aspartate (NMDA)
receptor. In this work the electronic structure, molecular electrostatic potential (MESP) and vibrational characteristics
of a set of C3 substituted 4-hydroxyquino-2-lone (HQ) derivatives, which act as Glycine/NMDA receptor antagonists, have been investigated
using the density functional calculations. In the optimized structures a substituent at the C3 site of HQ tends to adopt a helical structure. MESP investigations reveal that the ligands showing better inhibition activity
should possess electron-rich regions extending over the substituent and carbonyl group of HQ. A correlation of inhibitory
activity to the molecular electrostatic potential topography at the carbonyl oxygen as well as to the molecular electron density
topography turns out to be a significant output of the investigation.
Figure Quantam chemical approach has been employed to understand the reactivity of a set of hydroxyquinolone derivatives known for
their inhibition activity towards Glycine/NMDA receptor. Molecular electrostatic potential topography has been used as a tool
to understand the reactivity pattern 相似文献
7.
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
8.
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
9.
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
10.
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
11.
Frans T. I. Marx Johan H. L. Jordaan Hermanus C. M. Vosloo 《Journal of molecular modeling》2009,15(11):1371-1381
The productive self-metathesis reaction of 1-octene in the presence of the Phobcat precatalyst [RuCl2(Phoban-Cy)2(=CHPh)] using density functional theory was investigated and compared to the Grubbs 1 precatalyst [RuCl2(PCy3)2(=CHPh)]. At the GGA-PW91/DNP level, the geometry optimization of all the participating species and the PES scans of the various
activation and catalytic cycles in the dissociative mechanism were performed. The formation of the catalytically active heptylidene
species is kinetically and thermodynamically favored, while the formation of trans-tetradecene is thermodynamically favored.
相似文献
12.
Covalently bonded atoms, at least in Groups V–VII, may have regions of both positive and negative electrostatic potentials
on their surfaces. The positive regions tend to be along the extensions of the bonds to these atoms; the origin of this can
be explained in terms of the σ-hole concept. It is thus possible for such an atom in one molecule to interact electrostatically
with its counterpart in a second, identical molecule, forming a highly directional noncovalent bond. Several examples are
presented and discussed. Such “like-like” interactions could not be understood in terms of atomic charges assigned by any
of the usual procedures, which view a bonded atom as being entirely positive or negative.
Figure Calculated electrostatic potential on the surface of SCl2. The sulfur is in the foreground, the chlorines are at the back. Color ranges (kcal mol−1): purple negative, blue between 0 and 8, green between 8 and 15, yellow between 15 and 20, red more positive than 20. Note that the sulfur has regions of both positive (red) and negative (purple) electrostatic potential 相似文献
13.
Calvete MJ Dini D Hanack M Sancho-García JC Chen W Ji W 《Journal of molecular modeling》2006,12(5):543-550
The axially substituted binuclear GaCl/GaCl phthalocyanine 1 with an unsymmetrical pattern of substitution has been prepared and its nonlinear optical (NLO) properties determined. The resulting binuclear complex retains approximately the same transition energies of monomeric (RO)8PcGaCl as far as the linear optical spectrum is concerned, although 1 has a double concentration of central atoms per molecule and an enlarged conjugated ligand. The lack of significant spectral shifts in passing from mononuclear to binuclear complexes has been rationalized theoretically by means of density functional theory calculations. The purpose of the present study is to determine whether binuclearity affects the optical limiting behavior of 1 with respect to monomeric (RO)8PcGaCl in the NLO regime determined by nanosecond laser pulses.
Figure Bis axially substituted binuclear phthalocyanine: synthesis, DFT calculations and NLO properties
Dedicated to Professor Dr. Paul von Ragué Schleyer on the occasion of his 75th birthday. 相似文献
14.
Effective force fields for Ni-C interactions developed by Yamaguchi and Maruyama for the formation of metallofullerenes are
modified to simulate the catalyzed growth of single-wall carbon nanotubes on Nin clusters with n >20, and the reactive empirical bond order Brenner potential for C-C interactions is also revised to include the effect of
the metal atoms on such interactions.
Figure Force field parameters for carbon-metal interactions obtained from DFT calculations in small clusters. 相似文献
15.
Life has adapted to most environments on earth, including low and high temperature niches. The increased catalytic efficiency
and thermoliability observed for enzymes from organisms living in constantly cold regions when compared to their mesophilic
and thermophilic cousins are poorly understood at the molecular level. Uracil DNA glycosylase (UNG) from cod (cUNG) catalyzes
removal of uracil from DNA with an increased kcat and reduced Km relative to its warm-active human (hUNG) counterpart. Specific issues related to DNA repair and substrate binding/recognition
(Km) are here investigated by continuum electrostatics calculations, MD simulations and free energy calculations. Continuum electrostatic
calculations reveal that cUNG has surface potentials that are more complementary to the DNA potential at and around the catalytic
site when compared to hUNG, indicating improved substrate binding. Comparative MD simulations combined with free energy calculations
using the molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) method show that large opposing energies are involved
when forming the enzyme-substrate complexes. Furthermore, the binding free energies obtained reveal that the Michaelis-Menten
complex is more stable for cUNG, primarily due to enhanced electrostatic properties, suggesting that energetic fine-tuning
of electrostatics can be utilized for enzymatic temperature adaptation. Energy decomposition pinpoints the residual determinants
responsible for this adaptation.
Figure Electrostatic isosurfaces of cod uracil DNA glycosylase in complex with double stranded DNA 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.
Effects of explicit consideration of charges displaced from atomic sites due to atomic orbital hybridization called hybridization-displaced
charges (HDC) on dipole moments and surface molecular electrostatic potentials of certain radicals and their complexes with
closed-shell molecules have been studied. HDC were computed for several radicals and their complexes at the B3LYP/6–31G**
level of theory. At this level, HDC consist of three point charges associated with hydrogen atoms and seven point charges
associated with heavy atoms belonging to the second row of the periodic table. HDC are so calculated that the contribution
of each atom to the component of molecular dipole moment arising due to atomic orbital hybridization is preserved. It is found
that dipole moments and electrostatic potentials of the systems studied here can be obtained with a significantly improved
accuracy using a combination of Mulliken charges and HDC over that obtained by Mulliken charges only.
Figure Surface MEP map of H2O-HO· radical complex obtained using Mulliken charges combined with HDC 相似文献
18.
A pattern recognition algorithm for the alignment of drug-like molecules has been implemented. The method is based on the
calculation of quantum mechanical derived local properties defined on a molecular surface. This approach has been shown to
be very useful in attempting to derive generalized, non-atom based representations of molecular structure. The visualization
of these surfaces is described together with details of the methodology developed for their use in molecular overlay and similarity
calculations. In addition, this paper also introduces an additional local property, the local curvature (C
L), which can be used together with the quantum mechanical properties to describe the local shape. The method is exemplified
using some problems representing common tasks encountered in molecular similarity.
Figure Molecular surfaces for Lorazepam (left) and Diazepam (right) 相似文献
19.
The geometric and electronic structure of tetracyanoethylene (TCNE)-aniline (donor-acceptor type) complex has been investigated
in gas phase using ab initio and time dependent density functional theory calculations. Both the above calculations predict a composed structure for the
complex, in which the interacting site is a C≡N and C=C bond center in the TCNE and, –NH2 and π-electrons of aniline. The N atom of aniline is oriented toward the TCNE molecule. The charge transfer transition energy,
estimated by calculating the ground-to-excited state transition electric dipole moments of the complex, agree well with the
reported experimental value in chloroform medium.
TCNE-aniline at ground state. TCNE-aniline at excited state 相似文献
20.
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