scholarly journals An ab-initio study of pyrrole and imidazole arylamides

2013 ◽  
Vol 78 (11) ◽  
pp. 1789-1795
Author(s):  
Ara Abramyan ◽  
Zhiwei Liu ◽  
Vojislava Pophristic
Keyword(s):  
Dna Binding ◽  
Force Field ◽  
Dna Sequences ◽  
Density Functional ◽  
Md Simulations ◽  
Building Blocks ◽  
Amide Bond ◽  
Amide Bonds ◽  
Force Field Parameters ◽  
Arylamide Foldamers

Arylamide foldamers have been shown to have a number of biological and medicinal applications. For example, a class of pyrrole-imidazole polyamide foldamers is capable of binding specific DNA sequences and preventing development of various gene disorders, most importantly cancer. Molecular dynamics (MD) simulations can provide crucial details in understanding the atomic level events related to foldamer/DNA binding. An important first step in the accurate simulation of these foldamer/DNA systems is the reparametrization of force field parameters for torsion around the aryl-amide bonds. Here we highlight our Density Functional Theory (DFT) potential energy profiles and derived force field parameters for four aryl-amide bond types for the pyrrole and imidazole building blocks extensively used in foldamer design for the DNA-binding polyamides. These results contribute to developing of computational tools for an appropriate molecular modeling of pyrrole-imidazole polyamide/DNA binding, and provide an insight into the chemical factors that influence the flexibility of the pyrrole-imidazole polyamides, and their binding to DNA.

scholarly journals Electronic Effect on the Molecular Motion of Aromatic Amides: Combined Studies Using VT-NMR and Quantum Calculations

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2294 ◽  
Author(s):  
Sungsoo Kim ◽  
Jungyu Kim ◽  
Jieun Kim ◽  
Daeun Won ◽  
Suk-Kyu Chang ◽  
...  
Keyword(s):  
Aromatic Compounds ◽  
Density Functional ◽  
Electronic Effect ◽  
Variable Temperature ◽  
Rotational Barrier ◽  
Amide Bond ◽  
Theoretical Research ◽  
Quantum Calculations ◽  
Amide Bonds ◽  
Barrier Energy

Rotational barrier energy studies to date have focused on the amide bond of aromatic compounds from a kinetic perspective using quantum calculations and nuclear magnetic resonance (NMR). These studies provide valuable information, not only regarding the basic conformational properties of amide bonds but also the molecular gear system, which has recently gained interest. Thus, we investigate the precise motion of the amide bonds of two aromatic compounds using an experimental rotational barrier energy estimation by NMR experiments and a theoretical evaluation of the density functional theory calculation. The theoretical potential energy surface scan method combined with the quadratic synchronous transit 3 method and consideration of additional functional group rotation with optimization and frequency calculations support the results of the variable temperature 1H NMR, with deviations of less than 1 kcal/mol. This detailed experimental and theoretical research strongly supports molecular gear motion in the aromatic amide system, and the difference in kinetic energy indicates that the electronic effect from the aromatic structure has a key role in conformational movements at different temperatures. Our study provides an enhanced basis for future amide structural dynamics research.

Uncertainty Quantification in MD Simulations. Part II: Bayesian Inference of Force-Field Parameters

2012 ◽  
Vol 10 (4) ◽  
pp. 1460-1492 ◽  
Author(s):  
F. Rizzi ◽  
H. N. Najm ◽  
B. J. Debusschere ◽  
K. Sargsyan ◽  
M. Salloum ◽  
...  
Keyword(s):  
Bayesian Inference ◽  
Force Field ◽  
Uncertainty Quantification ◽  
Md Simulations ◽  
Force Field Parameters

scholarly journals Development and Testing of an All-Atom Force Field for Diketopyrrolopyrrole Polymers with Conjugated Substituents

2020 ◽  
Author(s):  
Vivek Sundaram ◽  
Alexey V. Lyulin ◽  
Björn Baumeier
Keyword(s):  
Force Field ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Building Blocks ◽  
Variable Number ◽  
Polymer Chains ◽  
Relaxation Processes ◽  
Polymer Backbone ◽  
Dynamics Simulations ◽  
The Individual

We develop an all-atom force field for a series of diketopyrrolopyrrole polymers with two aromatic pyridine substituents and variable number of pi-conjugated thiophene units in the backbone, used as donor material in organic photovoltaic devices. Available intra-fragment parameterizations of the individual fragment building blocks are combined with inter-fragment bonded and non-bonded parameters explicitly derived from density-functional theory calculations. To validate the force field we perform classical molecular dynamics simulations of single polymer chains with 1, 2, and 3 thiophenes in good and bad solvents, and of melts. We observe the expected dependence of the chain conformation on the solvent quality, with the chain collapsing in water, and swelling in chloroform. The glass transition temperature for the polymer melts is found to be in the range of 340K to 370K. Analysis of the mobility of the conjugated segments in the polymer backbone reveals two relaxation processes: a fast one with a characteristic time at room temperature on the order of 10ps associated with nearly harmonic vibrations and a slow one on the order of 100 associated with temperature activated cis-trans transitions.

scholarly journals Intermolecular Force Field Parameters Optimization for Computer Simulations of CH4in ZIF-8

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Phannika Kanthima ◽  
Pikul Puphasuk ◽  
Tawun Remsungnen
Keyword(s):  
Force Field ◽  
Md Simulations ◽  
Binding Energies ◽  
Parameters Optimization ◽  
Interaction Energies ◽  
Intermolecular Force ◽  
Amber Force Field ◽  
De Algorithm ◽  
Force Field Parameters ◽  
Structural Behaviors

The differential evolution (DE) algorithm is applied for obtaining the optimized intermolecular interaction parameters between CH4and 2-methylimidazolate ([C4N2H5]−) using quantum binding energies of CH4-[C4N2H5]−complexes. The initial parameters and their upper/lower bounds are obtained from the general AMBER force field. The DE optimized and the AMBER parameters are then used in the molecular dynamics (MD) simulations of CH4molecules in the frameworks of ZIF-8. The results show that the DE parameters are better for representing the quantum interaction energies than the AMBER parameters. The dynamical and structural behaviors obtained from MD simulations with both sets of parameters are also of notable differences.

scholarly journals Synthesis, Biological Activity, and Molecular Dynamics Study of Novel Series of a Trimethoprim Analogs as Multi-Targeted Compounds: Dihydrofolate Reductase (DHFR) Inhibitors and DNA-Binding Agents

2021 ◽  
Vol 22 (7) ◽  
pp. 3685
Author(s):  
Agnieszka Wróbel ◽  
Maciej Baradyn ◽  
Artur Ratkiewicz ◽  
Danuta Drozdowska
Keyword(s):  
Dna Binding ◽  
Dihydrofolate Reductase ◽  
Solid Phase ◽  
Binding Capacity ◽  
Minor Groove ◽  
Amide Bond ◽  
Amide Bonds ◽  
Binding Agents ◽  
Pbr322 Plasmid ◽  
A Minor

Eighteen previously undescribed trimethoprim (TMP) analogs containing amide bonds (1–18) were synthesized and compared with TMP, methotrexate (MTX), and netropsin (NT). These compounds were designed as potential minor groove binding agents (MGBAs) and inhibitors of human dihydrofolate reductase (hDHFR). The all-new derivatives were obtained via solid phase synthesis using 4-nitrophenyl Wang resin. Data from the ethidium displacement test confirmed their DNA-binding capacity. Compounds 13–14 (49.89% and 43.85%) and 17–18 (41.68% and 42.99%) showed a higher binding affinity to pBR322 plasmid than NT. The possibility of binding in a minor groove as well as determination of association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT)2, and poly (dG-dC)2. With the exception of compounds 9 (IC50 = 56.05 µM) and 11 (IC50 = 55.32 µM), all of the compounds showed better inhibitory properties against hDHFR than standard, which confirms that the addition of the amide bond into the TMP structures increases affinity towards hDHFR. Derivatives 2, 6, 13, 14, and 16 were found to be the most potent hDHFR inhibitors. This molecular modelling study shows that they interact strongly with a catalytically important residue Glu-30.

Development of Cu2+-Based Distance Methods and Force Field Parameters for the Determination of PNA Conformations and Dynamics by EPR and MD Simulations

2020 ◽  
Vol 124 (35) ◽  
pp. 7544-7556
Author(s):  
Austin Gamble Jarvi ◽  
Artur Sargun ◽  
Xiaowei Bogetti ◽  
Junmei Wang ◽  
Catalina Achim ◽  
...  
Keyword(s):  
Force Field ◽  
Md Simulations ◽  
Distance Methods ◽  
Force Field Parameters

scholarly journals Inchworm stepping of Myc-Max heterodimer protein diffusion along DNA

2020 ◽  
Author(s):  
Liqiang Dai ◽  
Jin Yu
Keyword(s):  
Dna Binding ◽  
Dna Sequences ◽  
Leucine Zipper ◽  
Control Cell ◽  
Md Simulations ◽  
Coarse Grained ◽  
Protein Diffusion ◽  
Hydrogen Bond Interactions ◽  
Diffusion Dynamics ◽  
Dna Strand

AbstractOncogenic protein Myc serves as a transcription factor to control cell metabolisms. Myc dimerizes via leucine zipper with its associated partner protein Max to form a heterodimer structure, which then binds target DNA sequences to regulate gene transcription. The regulation depends on by Myc-Max binding to DNA and searching for target sequences via diffusional motions along DNA. Here, we conduct structure-based molecular dynamics (MD) simulations to investigate the diffusion dynamics of the Myc-Max heterodimer along DNA. We found that the heterodimer protein slides on the DNA in a rotation-uncoupled manner in coarse-grained simulations, as its two helical DNA binding basic regions (BRs) alternate between open and closed conformations via inchworm stepping motions. In such motions, the two BRs of the heterodimer step across the DNA strand one by one, with step sizes up about half of a DNA helical pitch length. Atomic MD simulations of the Myc-Max heterodimer in complex with DNA have also been conducted. Hydrogen bond interactions reveal between the two BRs and two complementary DNA strands, respectively. In the non-specific DNA binding, the BR shows an onset of stepping on one association DNA strand and dissociating from the complementary strand. Overall, our simulation studies suggest that the inchworm stepping motions of the Myc-Max heterodimer can be achieved during the protein diffusion along DNA.

scholarly journals Density Functional Studies on Secondary Amides: Role of Steric Factors in Cis/Trans Isomerization

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2455 ◽  
Author(s):  
Balmukund Thakkar ◽  
John Svendsen ◽  
Richard Engh
Keyword(s):  
Density Functional ◽  
Amide Bond ◽  
Steric Effects ◽  
Amide Bonds ◽  
Functional Studies ◽  
Bond Rotation ◽  
Trans Isomerization ◽  
Wide Range ◽  
Potential Applications ◽  
Secondary Amides

Cis/trans isomerization of amide bonds is a key step in a wide range of biological and synthetic processes. Occurring through C-N amide bond rotation, it also coincides with the activation of amides in enzymatic hydrolysis. In recently described QM studies of cis/trans isomerization in secondary amides using density functional methods, we highlighted that a peptidic prototype, such as glycylglycine methyl ester, can suitably represent the isomerization and complexities arising out of a larger molecular backbone, and can serve as the primary scaffold for model structures with different substitution patterns in order to assess and compare the steric effect of the substitution patterns. Here, we describe our theoretical assessment of such steric effects using tert-butyl as a representative bulky substitution. We analyze the geometries and relative stabilities of both trans and cis isomers, and effects on the cis/trans isomerization barrier. We also use the additivity principle to calculate absolute steric effects with a gradual increase in bulk. The study establishes that bulky substitutions significantly destabilize cis isomers and also increases the isomerization barrier, thereby synergistically hindering the cis/trans isomerization of secondary amides. These results provide a basis for the rationalization of kinetic and thermodynamic properties of peptides with potential applications in synthetic and medicinal chemistry.

scholarly journals Development and Testing of an All-Atom Force Field for Diketopyrrolopyrrole Polymers with Conjugated Substituents

2020 ◽  
Author(s):  
Vivek Sundaram ◽  
Alexey V. Lyulin ◽  
Björn Baumeier
Keyword(s):  
Force Field ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Building Blocks ◽  
Variable Number ◽  
Polymer Chains ◽  
Relaxation Processes ◽  
Polymer Backbone ◽  
Dynamics Simulations ◽  
The Individual

We develop an all-atom force field for a series of diketopyrrolopyrrole polymers with two aromatic pyridine substituents and variable number of pi-conjugated thiophene units in the backbone, used as donor material in organic photovoltaic devices. Available intra-fragment parameterizations of the individual fragment building blocks are combined with inter-fragment bonded and non-bonded parameters explicitly derived from density-functional theory calculations. To validate the force field we perform classical molecular dynamics simulations of single polymer chains with 1, 2, and 3 thiophenes in good and bad solvents, and of melts. We observe the expected dependence of the chain conformation on the solvent quality, with the chain collapsing in water, and swelling in chloroform. The glass transition temperature for the polymer melts is found to be in the range of 340K to 370K. Analysis of the mobility of the conjugated segments in the polymer backbone reveals two relaxation processes: a fast one with a characteristic time at room temperature on the order of 10ps associated with nearly harmonic vibrations and a slow one on the order of 100 associated with temperature activated cis-trans transitions.

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