scholarly journals Residue Interactions Affecting The Deprotonation of Internal Guanine Moieties In Oligodeoxyribonucleotides, Calculated By FMO Methods

2021 ◽  
Author(s):  
Absalom Zamorano-Carrillo ◽  
Gerardo Arreola-Jardón ◽  
Reynaldo C. Pless ◽  
Julio C. González-Olvera
Keyword(s):  
Decomposition Analysis ◽  
Pair Interaction ◽  
Original Position ◽  
Electric Field Effect ◽  
Free Energies ◽  
Hydronium Ion ◽  
Physical Experiments ◽  
Guanine Residue ◽  
Dna Chain ◽  
Good Agreement

Abstract The effect of vicinal molecular groups on the intrinsic acidity of a central guanine residue in short single-stranded DNA models, and the potentials exerted by the backbone and the nucleobases on the leaving proton were determined by the Fragment Molecular Orbital (FMO) method, in terms of quantum descriptors (QD) and pair interaction interfragment decomposition analysis (PIEDA). The acidity of the central guanine moiety decreased with increasing oligonucleotide length, in response to changes by less than1 eV in the ionization potential, global softness, electrophilicity index and electronegativity descriptors. The differences in these descriptors were majorly interpreted in terms of the electrostatic influence of the negative charges residing on the backbone of the molecule. Additionally, this electric-field effect was determined explicitly for the displacement of the test hydronium ion to a distance of 250 Å from its original position, resulting in good agreement with calculations of the variation in Gibbs free energies, obtained from physical experiments conducted on the identical oligonucleotide sequences. The reported results are useful for biophysical applications of deoxyriboligonucleotides containing guanine residues in order to induce local negative charges at specific positions in the DNA chain.

Partition Coefficients of Methylated DNA Bases Obtained from Free Energy Calculations with Molecular Electron Density Derived Atomic Charges.

2018 ◽  
Author(s):  
Alejandro Lara ◽  
Maximiliano Riquelme ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Electron Density ◽  
Partition Coefficients ◽  
Dna Bases ◽  
Atomic Charges ◽  
Free Energies ◽  
Solvation Model ◽  
Minimal Basis ◽  
Methylated Dna ◽  
Implicit Solvation Model ◽  
Good Agreement

<div> <div> <div> <p>Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have been also used to address the accuracy of force fields for various organic compounds and specifically the methylated DNA bases. In this study atomic charges were derived by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder) directly from the electron density obtained by electronic structure calculations in vac- uum, with an implicit solvation model or with explicit solvation taking the dynamics of the solute and the solvent into account. To test the ability of these charges to describe electrostatic interactions in force fields for condensed phases the original atomic charges of the AMBER99 force field were replaced with the new atomic charges and combined with different solvent models to obtain the hydration and chloroform solvation free energies by molecular dynamics simulations. Chloroform-water partition coefficients derived from the obtained free energies were compared to experimental and previously reported values obtained with the GAFF or the AMBER-99 force field. The results show that good agreement with experimental data is obtained when the polarization of the electron density by the solvent has been taken into account deriving the atomic charges of polar DNA bases and when the energy needed to polarize the electron den- sity of the solute has been considered in the transfer free energy. These results were further confirmed by hydration free energies of polar and aromatic amino acid side chain analogues. Comparison of the two partitioning methods Hirsheld-I and Minimal Basis Iterative Stockholder (MBIS) revealed some deficiencies in the Hirshfeld-I method related to nonexistent isolated anionic nitrogen pro-atoms used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the MBIS partitioning method accounting for polarization by the implicit solvation model are in good agreement with the experimental values. </p> </div> </div> </div>

THEORETICAL CALCULATION OF pKb VALUES FOR ANILINES AND SULFONAMIDE DRUGS IN AQUEOUS SOLUTION

2012 ◽  
Vol 11 (02) ◽  
pp. 283-295 ◽  
Author(s):  
BAHRAM GHALAMI-CHOOBAR ◽  
ALI GHIAMI-SHOMAMI ◽  
PARIA NIKPARSA
Keyword(s):  
Gas Phase ◽  
Continuum Model ◽  
Correlation Equation ◽  
Polarizable Continuum Model ◽  
Free Energies ◽  
Pcm Model ◽  
Solvation Models ◽  
Polarizable Continuum ◽  
Better Than ◽  
Good Agreement

In this work, calculations of p K b values have been performed for aniline and its substituted derivatives and sulfonamide drugs by using Gaussian 98 software package. Gas-phase energies were calculated with HF /6-31 G ** and B3LYP /6-31 G ** levels of theory. Free energies of solvation have been computed using the polarizable continuum model (PCM), conductor-like polarizable continuum model (CPCM) and the integral equation formalism-polarizable continuum model (IEFPCM) at the same levels which have been used for geometry determination in the gas-phase. The results show that the calculated p K b values using the B3LYP /6-31 G ** are better than those using the corresponding HF /6-31 G **. At first, the correlation equation was found to determine the p K b values of the investigated anilines. Then, this correlation equation was used to calculate the p K b values of the sulfonamide drugs. The results obtained indicate that the PCM model is a suitable solvation model for calculating p K b values in comparison to the other solvation models. For the investigated compounds a good agreement between the experimental and the calculated p K b values was also observed.

scholarly journals Nucleation barriers at corners for a cubic-to-tetragonal phase transformation

2015 ◽  
Vol 145 (4) ◽  
pp. 715-724 ◽  
Author(s):  
Peter Bella ◽  
Michael Goldman
Keyword(s):  
Phase Transformation ◽  
Tetragonal Phase ◽  
Scaling Law ◽  
Energetic Cost ◽  
Minimal Energy ◽  
Physical Experiments ◽  
Domain With A Corner ◽  
Appl Math ◽  
Good Agreement

We are interested in the energetic cost of a martensitic inclusion of volume V in austenite for the cubic-to-tetragonal phase transformation. In contrast with the work of Knüpfer, Kohn and Otto (Commun. Pure Appl. Math.66 (2013), 867–904), we consider a domain with a corner and obtain a better scaling law for the minimal energy (Emin ∼ min(V2/3, V7/9)). Our predictions are in good agreement with physical experiments where nucleation of martensite is usually observed near the corners of the specimen.

scholarly journals A thermodynamic description of metastable c-TiAlZrN coatings with triple spinodally decomposed domains

2017 ◽  
Vol 53 (2) ◽  
pp. 85-93 ◽  
Author(s):  
J. Zhou ◽  
L. Zhang ◽  
L. Chen ◽  
Y. Du ◽  
Z.K. Liu
Keyword(s):  
Experimental Data ◽  
Phase Equilibria ◽  
First Principles ◽  
Thermodynamic Description ◽  
Quantitative Description ◽  
Experimental Phase Equilibria ◽  
Free Energies ◽  
Calphad Technique ◽  
Important Input ◽  
Good Agreement

A critical thermodynamic assessment of the metastable c-TiAlZrN coatings, which are reported to spinodally decompose into triple domains, i.e., c-TiN, c-AlN, and c-ZrN, was performed via the CALculation of PHAse Diagram (CALPHAD) technique based on the limited experimental data as well as the first-principles computed free energies. The metastable c-TiAlZrN coatings were modeled as a pseudo-ternary phase consisting of c-TiN, c-AlN and c-ZrN species, and described using the substitutional solution model. The thermodynamic descriptions for the three boundary binaries were directly taken from either the CALPHAD assessment or the first-principles results available in the literature except for a re-adjustment of the pseudo-binary c-AlN/c-ZrN system based on the experimental phase equilibria in the pseudo-ternary system. The good agreement between the calculated phase equilibria and the experimental data over the wide temperature range was obtained, validating the reliability of the presently obtained thermodynamic descriptions for the c-TiAlZrN system. Based on the present thermodynamic description, different phase diagrams and thermodynamic properties can be easily predicted. It is anticipated that the present thermodynamic description of the metastable c-TiAlZrN coatings can serve as the important input for the later quantitative description of the microstructure evolution during service life.

scholarly journals Novel Pyrazolo[3,4-c]pyridine Antagonists with Nanomolar affinity for A1 / A3 Adenosine Receptors: Binding Kinetics and Exploration of their Binding Profile Using Mutagenesis Experiments, MD simulations and TI/MD calculations

2021 ◽  
Author(s):  
Margarita Stampelou ◽  
Anna Suchankova ◽  
Eva Tzortzini ◽  
Lakshiv Dhingra ◽  
Kerry Barkan ◽  
...  
Keyword(s):  
Drug Design ◽  
Transmembrane Helix ◽  
Rank Correlation ◽  
Membrane System ◽  
Md Simulations ◽  
Dissociation Rate ◽  
The Novel ◽  
Free Energies ◽  
Electronegative Group ◽  
Good Agreement

Drugs targeting the four adenosine receptor (AR) subtypes can provide “soft" treatment of various significant diseases. Even for the two experimentally resolved AR subtypes the description of the orthosteric binding area and structure-activity relationships of ligands remains a demanding task due to the high similar amino acids sequence but also the broadness and flexibility of the ARs binding area. The identification of new pharmacophoric moieties and nanomolar leads and the exploration of their binding area with mutagenesis and state-of-the-art computational methods useful also for drug design purposes remains a challenging aim for all ARs. Here, we identified several low nanomolar ligands and potent competitive antagonists against A1R / A3R, containing the novel pyrazolo[3,4-c]pyridine pharmacophore for ARs, from a screen of an in-house library of only 52 compounds, originally designed for anti-proliferative activity. We identified L2-L10, A15, A17 with 3-aryl, 7-anilino and a electronegative group at 5-position as low micromolar to low nanomolar A1R / A3R antagonists. A17 has for A1R Kd = 5.62 nM and a residence time (RT) 41.33 min and for A3R Kd = 13.5 nM, RT = 47.23 min. The kinetic data showed that compared to the not potent or mediocre congeners the active compounds have similar association, for example at A1R Kon = 13.97 x106 M-1 (A17) vs Kon = 3.36 x106 M-1 (A26) but much lower dissociation rate Koff = 0.024 min-1 (A17) vs 0.134 min-1 (A26). Using molecular dynamics (MD) simulations and mutagenesis experiments we investigated the binding site of A17 showing that it can interact with an array of residues in transmembrane helix 5 (TM5), TM6, TM7 of A1R or A3R including residues E5.30, E5.28, T7.35 in A1R instead of Q5.28, V5.30 , L7.35 in A3R. A striking observation for drug design purposes is that for L2506.51A the binding affinity of A17 significantly increased at A1R. A17 provides a lead representative of a promising series and by means of the Thermodynamics Integration coupled with MD simulations (TI/MD) method, first applied here on whole GPCR- membrane system and showing a very good agreement between calculated and experimental relative binding free energies for A1R and A3R (spearman rank correlation p = 0.82 and 0.84, respectively), and kinetic experiments can lead to ligands with improved profile against ARs.

Chemical Shift. VII. The Long-range Shielding Effects of the Cyano Group

1972 ◽  
Vol 50 (14) ◽  
pp. 2351-2356 ◽  
Author(s):  
J. W. ApSimon ◽  
H. Beierbeck ◽  
D. K. Todd
Keyword(s):  
Chemical Shift ◽  
Long Range ◽  
Field Effect ◽  
Cyano Group ◽  
Electric Field Effect ◽  
Minor Contribution ◽  
Anisotropy Effect ◽  
A Minor ◽  
Good Agreement ◽  
Shielding Effects

Using the methods described in parts I–VI of this series, we have examined the long-range shielding effects of the cyano group upon the C-18 and -19 methyl protons in several cyano-steroids and the ring protons in 2-endo- and 2-exo-cyanonorbornenes.It was found that the most important shielding mechanism of the cyano group is its electric field effect, with the magnetic anisotropy effect making at most a minor contribution to the screening. However, only in the cases of the cyano-steroids was good agreement obtained between the calculated and the experimental shifts.

Development and Applicability of Multiscale Multiphysics Integrated Simulator for Tsunami

2019 ◽  
Vol 14 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Taro Arikawa ◽  
Yu Chida ◽  
Katsumi Seki ◽  
Tomohiro Takagawa ◽  
Kenichiro Shimosako ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Structural Damage ◽  
Numerical Results ◽  
Structural Deformation ◽  
Local Conditions ◽  
Physical Experiments ◽  
The Stability ◽  
Good Agreement

In this research, we develop a numerical fluid simulator coupled with a structural analysis. The purpose of this system is to efficiently calculate all stages of a tsunami from source to runup, including structural deformation. We also investigate the stability of breakwaters at Kamaishi port. The numerical results are compared with physical experiments, revealing good agreement. The system is applied to the local conditions at Kamaishi port to verify its applicability. Most of the breakwaters are washed away, which is similar to the actual reported damage, indicating that the proposed system can effectively reproduce tsunami structural damage.

Numerical Modeling of Gasdynamic Processes and Processes of Deformation in Compressor of Model Test Bench of the Gas-Distributing Unit

2015 ◽  
Vol 799-800 ◽  
pp. 865-869 ◽  
Author(s):  
Vladimir Yakovlevich Modorskiy ◽  
Arthur Fadanisovich Shmakov
Keyword(s):  
Numerical Modeling ◽  
Model Test ◽  
Strain State ◽  
Test Bench ◽  
State Structure ◽  
Stress Strain ◽  
Stress Strain State ◽  
Physical Experiments ◽  
Heat Loads ◽  
Good Agreement

In this work results of numerical modeling of the gasdynamic processes and processes of deformation proceeding in the compressor of the model test bench of the gas-distributing unit are provided. Fields of pressure and temperatures, and also component of the stress-strain state structure taking into account the imported gasdynamic and heat loads are received. A good agreement with data of physical experiments is received.

SUBSTITUTIONAL AND CONFIGURATIONAL EFFECTS ON CHEMICAL SHIFT IN PYRANOID CARBOHYDRATE DERIVATIVES

1965 ◽  
Vol 43 (7) ◽  
pp. 2059-2070 ◽  
Author(s):  
R. U. Lemieux ◽  
J. D. Stevens
Keyword(s):  
Chemical Shift ◽  
Long Range ◽  
Chemical Shifts ◽  
Coupling Constants ◽  
Equatorial Orientation ◽  
Free Energies ◽  
Bonding Interaction ◽  
Conformational Properties ◽  
Good Agreement ◽  
Shielding Effects

The effects of long-range and virtual long-range coupling on the observed spectra of acetylated hexopyranoses and pentopyranoses are examined. Use is made of both spin decoupling and specific deuteration for the assignment of signals. It is seen that specific solvent effects on chemical shift can be superior to increasing the applied magnetic field for the resolution of the signals of closely related protons. The alteration of virtual long-range coupling effects in these ways can be useful in the diagnosis of spectra. Empirical rules are derived for estimating the long-range shielding effects which occur on changing configurations. It is seen that the inversion of a center can lead to deshielding of axial protons and to shielding of equatorial protons at other centers relative to the chemical shifts observed in reference compounds wherein all the acetoxy groups are in equatorial orientation. The effects in several cases result in equatorial protons giving their signal to higher field than chemically similar but axial protons. The conformational properties of pentopyranose tetraacetates as estimated from chemical shifts and coupling constants are seen to be in good agreement with expectations based on non-bonding interaction free energies. As expected, 2-deoxy-β-D-ribopyranose triacetate has the 1C-conformation when dissolved in chloroform.

Sign in / Sign up

Export Citation Format

Share Document