scholarly journals Computational Evaluation of 2-Phenyl-4H-chromen-4-one Analogues as Antihistamines: Potential HistamineN-Methyltransferase (HMT) Inhibitors

2009 ◽  
Vol 6 (4) ◽  
pp. 1009-1016
Author(s):  
Shikha S. Dave ◽  
Anjali M. Rahatgaonkar
Keyword(s):  
Binding Energy ◽  
Active Sites ◽  
Competitive Inhibitor ◽  
Binding Energies ◽  
Human Beings ◽  
High Concentration ◽  
Major Pathway ◽  
Methyl Transferase ◽  
Computational Evaluation ◽  
Active Site Cavity

Abnormal release of histamine, which is present in relatively high concentration in the lungs, causes serious allergic vasoconstriction and anaphylactic manifestation in human beings. In mammals, a major pathway of histamine metabolism in the lungs is mediated by histamineN-methyl transferase (HMT) and diamine oxidase. The need to design a strategy of mechanistic computational evaluation of protein-ligand affinityi.e. HMT- 2-phenyl-4H-chromen-4-ones, protein complex binding energy has been established. A library of synthesized 2-phenyl-4H-chromen-4-ones was docked into the active site cavity of target protein, HMT (Pdb: 2aot). The high-resolution crystal structure of HMT complex with the competitive inhibitorN[2 (benzhydryloxy)ethyl]N N-Dimethylamine (Diphenhydramine) revealed a protein with a highly confined binding region that could be targeted in the design of specific anti-histamines. The validation of docking programme by Potential Mean Force was compared with binding energy results of known ligands in the active sites of HMT, diphenhydramine / benadryl, promethazine, cyproheptadine, trimeton / aviletc. All the synthesized chromone derivatives showed comparable negative binding energies pointing towards the fact that these molecules could be potent antihistamines.

scholarly journals Photolabelling of Salmonella typhimurium LT2 sialidase. Identification of a peptide with a predicted structural similarity to the active sites of influenza-virus sialidases

1992 ◽  
Vol 285 (3) ◽  
pp. 957-964 ◽  
Author(s):  
T G Warner ◽  
R Harris ◽  
R McDowell ◽  
E R Vimr
Keyword(s):  
Salmonella Typhimurium ◽  
Active Site ◽  
Influenza A ◽  
Active Sites ◽  
Enzyme Inhibitors ◽  
Structural Similarity ◽  
Competitive Inhibitor ◽  
Beta Sheets ◽  
Sialidase Inhibitor ◽  
Active Site Cavity

The sialidase from Salmonella typhimurium LT2 was characterized by using photoaffinity-labelling techniques. The well-known sialidase inhibitor 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non- 2-enonic acid (Neu5Ac2en) was modified to contain an amino group at C-9, which permitted the incorporation of 4-azidosalicylic acid in amide linkage at this position. Labelling of the purified protein with the radioactive (125I) photoprobe was determined to be highly specific for a region within the active-site cavity. This conclusion was based on the observation that the competitive inhibitor Neu5Ac2en in the photolysis mixture prevented labelling of the protein. In contrast, compounds with structural and chemical features similar to the probe and Neu5Ac2en, but which were not competitive enzyme inhibitors, did not affect the photolabelling of the protein. The peptide interacting with the probe was identified by CNBr treatment of the labelled protein, followed by N-terminal sequence analysis. Inspection of the primary structure of the protein, predicted from the cloned structural gene for the sialidase [Hoyer, Hamilton, Steenbergen & Vimr (1992) Mol. Microbiol. 6, 873-884] revealed that the label was incorporated into a 9.6 kDa fragment situated within the terminal third of the molecule near the C-terminal end. Secondary-structural predictions using the Garnier-Robson algorithm [Garnier, Osguthorpe & Robson (1978) J. Mol. Biol. 120, 97-120] of the labelled peptide revealed a structural similarity to the active site of influenza-A- and Sendai-HN-virus sialidases with a repetitive series of alternating beta-sheets connected with loops.

On the Adsorption of Aspartate Derivatives to Calcite Surfaces in Aqueous Environment

2020 ◽  
Author(s):  
Robert Stepic ◽  
Lara Jurković ◽  
Ksenia Klementyeva ◽  
Marko Ukrainczyk ◽  
Matija Gredičak ◽  
...  
Keyword(s):  
Active Sites ◽  
Realistic Model ◽  
Binding Energies ◽  
Inhibition Mechanism ◽  
Aqueous Environment ◽  
Binding Modes ◽  
Carboxylate Groups ◽  
Dissolved Ions ◽  
Living Organisms ◽  
Dynamics Simulations

In many living organisms, biomolecules interact favorably with various surfaces of calcium carbonate. In this work, we have considered the interactions of aspartate (Asp) derivatives, as models of complex biomolecules, with calcite. Using kinetic growth experiments, we have investigated the inhibition of calcite growth by Asp, Asp2 and Asp3.This entailed the determination of a step-pinning growth regime as well as the evaluation of the adsorption constants and binding free energies for the three species to calcite crystals. These latter values are compared to free energy profiles obtained from fully atomistic molecular dynamics simulations. When using a flat (104) calcite surface in the models, the measured trend of binding energies is poorly reproduced. However, a more realistic model comprised of a surface with an island containing edges and corners, yields binding energies that compare very well with experiments. Surprisingly, we find that most binding modes involve the positively charged, ammonium group. Moreover, while attachment of the negatively charged carboxylate groups is also frequently observed, it is always balanced by the aqueous solvation of an equal or greater number of carboxylates. These effects are observed on all calcite features including edges and corners, the latter being associated with dominant affinities to Asp derivatives. As these features are also precisely the active sites for crystal growth, the experimental and theoretical results point strongly to a growth inhibition mechanism whereby these sites become blocked, preventing further attachment of dissolved ions and halting further growth.

Catalytic Neutralization of Naphthenic Acid from Petroleum Crude Oil by Using Cerium Oxide Catalyst and 2- Methylimidazole in Polyethylene Glycol

2020 ◽  
Vol 13 ◽  
Author(s):  
Norshahidatul Akmar Mohd Shohaimi ◽  
Norfakhriah Jelani ◽  
Ahmad Zamani Ab Halim ◽  
Nor Hakimin Abdullah ◽  
Nurasmat Mohd Shukri
Keyword(s):  
Polyethylene Glycol ◽  
Crude Oil ◽  
Cerium Oxide ◽  
Active Sites ◽  
Naphthenic Acid ◽  
Naphthenic Acids ◽  
Catalyst Loading ◽  
High Concentration ◽  
Oil Refineries ◽  
Al2o3 Catalyst

: The presence of relatively high naphthenic acid in crude oil may contribute to the major corrosion in oil pipelines and distillation units in crude oil refineries. Thus, high concentration Naphthenic Acids crude oil is considered tobe of low quality and is marketed at lower prices. In order to overcome this problem, neutralization method had been developed to reduce the TAN value in crude oil. In this study, crude oil from Petronas Penapisan Melaka was investigated. The parameters studied were reagent concentration, catalyst loading, calcination temperature and reusability of the potential catalyst. Basic chemical used were 2- methylimidazole in polyethylene glycol (PEG 600) with concentration 100, 500 and 1000 ppm. Cerium oxide-based catalysts supported onto alumina prepared with different calcination temperatures. The catalyst was characterized by using Brunauer-Emmett-Teller (BET), Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetry Analysis-Differential Thermal Gravity (TGA-DTG) to study physical properties of the catalyst. The Ce/Al2O3 catalyst calcined at 1000°C was the best catalyst due to larger surface area formation which lead to increment of active sites thus will boost the catalytic activity. The result showed that the Ce/Al2O3 catalyst meet Petronas requirement as the TAN value reduced to 0.6 mgKOH/g from original TAN value of 4.22 mgKOH/g. The best reduction of TAN was achieved by using catalyst loading of 0.39% and reagent of 1000 ppm.

scholarly journals Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1051
Author(s):  
Edgardo Becerra ◽  
Giovanny Aguilera-Durán ◽  
Laura Berumen ◽  
Antonio Romo-Mancillas ◽  
Guadalupe García-Alcocer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Binding Sites ◽  
Adenosine Monophosphate ◽  
Competitive Inhibitor ◽  
Umbrella Sampling ◽  
Coarse Grained ◽  
Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

A DFT study of spherands containing five anisyl groups — Highly preorganized to bind the alkali metal

2006 ◽  
Vol 84 (8) ◽  
pp. 1045-1049 ◽  
Author(s):  
Shabaan AK Elroby ◽  
Kyu Hwan Lee ◽  
Seung Joo Cho ◽  
Alan Hinchliffe
Keyword(s):  
Density Functional Theory ◽  
Binding Energy ◽  
Density Functional ◽  
Ionic Radius ◽  
Binding Energies ◽  
Cavity Size ◽  
X Ray Diffraction ◽  
Functional Theory ◽  
X Ray ◽  
Good Agreement

Although anisyl units are basically poor ligands for metal ions, the rigid placements of their oxygens during synthesis rather than during complexation are undoubtedly responsible for the enhanced binding and selectivity of the spherand. We used standard B3LYP/6-31G** (5d) density functional theory (DFT) to investigate the complexation between spherands containing five anisyl groups, with CH2–O–CH2 (2) and CH2–S–CH2 (3) units in an 18-membered macrocyclic ring, and the cationic guests (Li+, Na+, and K+). Our geometric structure results for spherands 1, 2, and 3 are in good agreement with the previously reported X-ray diffraction data. The absolute values of the binding energy of all the spherands are inversely proportional to the ionic radius of the guests. The results, taken as a whole, show that replacement of one anisyl group by CH2–O–CH2 (2) and CH2–S–CH2 (3) makes the cavity bigger and less preorganized. In addition, both the binding and specificity decrease for small ions. The spherands 2 and 3 appear beautifully preorganized to bind all guests, so it is not surprising that their binding energies are close to the parent spherand 1. Interestingly, there is a clear linear relation between the radius of the cavity and the binding energy (R2 = 0.999).Key words: spherands, preorganization, density functional theory, binding energy, cavity size.

scholarly journals Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19)

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 460
Author(s):  
Amr El-Demerdash ◽  
Ahmed M. Metwaly ◽  
Afnan Hassan ◽  
Tarek Mohamed Abd El-Aziz ◽  
Eslam B. Elkaeed ◽  
...  
Keyword(s):  
In Silico ◽  
Active Sites ◽  
Specific Treatment ◽  
Aqueous Solubility ◽  
Maximum Tolerated Dose ◽  
Binding Energies ◽  
Log P ◽  
Binding Affinities ◽  
Structural Protein ◽  
Guanidine Alkaloids

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (ΔG = −8.05 kcal/mol), nucleocapsid phosphoprotein (ΔG = −6.49 kcal/mol), and nsp10 (ΔG = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (ΔG = −7.99 kcal/mol), spike glycoproteins (ΔG = −6.95 kcal/mol), and nucleocapsid phosphoprotein (ΔG = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and 13 showed promising docking, ADMET, toxicity and MD results which open the door for further investigations for them against SARS-CoV-2.

scholarly journals np-Pair Correlations in the Isovector Pairing Model

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1405
Author(s):  
Feng Pan ◽  
Yingwen He ◽  
Lianrong Dai ◽  
Chong Qi ◽  
Jerry P. Draayer
Keyword(s):  
Binding Energy ◽  
Occupation Number ◽  
Mean Field ◽  
Energy Difference ◽  
Binding Energies ◽  
Pair Correlations ◽  
Isospin Symmetry Breaking ◽  
Pairing Model ◽  
Proton Pairing ◽  
Spin Basis

A diagonalization scheme for the shell model mean-field plus isovector pairing Hamiltonian in the O(5) tensor product basis of the quasi-spin SUΛ(2) ⊗ SUI(2) chain is proposed. The advantage of the diagonalization scheme lies in the fact that not only can the isospin-conserved, charge-independent isovector pairing interaction be analyzed, but also the isospin symmetry breaking cases. More importantly, the number operator of the np-pairs can be realized in this neutron and proton quasi-spin basis, with which the np-pair occupation number and its fluctuation at the J = 0+ ground state of the model can be evaluated. As examples of the application, binding energies and low-lying J = 0+ excited states of the even–even and odd–odd N∼Z ds-shell nuclei are fit in the model with the charge-independent approximation, from which the neutron–proton pairing contribution to the binding energy in the ds-shell nuclei is estimated. It is observed that the decrease in the double binding-energy difference for the odd–odd nuclei is mainly due to the symmetry energy and Wigner energy contribution to the binding energy that alter the pairing staggering patten. The np-pair amplitudes in the np-pair stripping or picking-up process of these N = Z nuclei are also calculated.

scholarly journals Screening marine algae metabolites as high-affinity inhibitors of SARS-CoV-2 main protease (3CLpro): an in silico analysis to identify novel drug candidates to combat COVID-19 pandemic

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Ghazala Muteeb ◽  
Adil Alshoaibi ◽  
Mohammad Aatif ◽  
Md. Tabish Rehman ◽  
M. Zuhaib Qayyum
Keyword(s):  
Hydrophobic Interactions ◽  
In Silico Analysis ◽  
Salt Bridge ◽  
Competitive Inhibitor ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
In Vivo Studies ◽  
Energy Calculation

AbstractThe recent dissemination of SARS-CoV-2 from Wuhan city to all over the world has created a pandemic. COVID-19 has cost many human lives and created an enormous economic burden. Although many drugs/vaccines are in different stages of clinical trials, still none is clinically available. We have screened a marine seaweed database (1110 compounds) against 3CLpro of SARS-CoV-2 using computational approaches. High throughput virtual screening was performed on compounds, and 86 of them with docking score <  − 5.000 kcal mol−1 were subjected to standard-precision docking. Based on binding energies (< − 6.000 kcal mol−1), 9 compounds were further shortlisted and subjected to extra-precision docking. Free energy calculation by Prime-MM/GBSA suggested RC002, GA004, and GA006 as the most potent inhibitors of 3CLpro. An analysis of ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of RC002, GA004, and GA006 indicated that only RC002 (callophysin A, from red alga Callophycus oppositifolius) passed Lipinski’s, Veber’s, PAINS and Brenk’s filters and displayed drug-like and lead-like properties. Analysis of 3CLpro-callophysin A complex revealed the involvement of salt bridge, hydrogen bonds, and hydrophobic interactions. callophysin A interacted with the catalytic residues (His41 and Cys145) of 3CLpro; hence it may act as a mechanism-based competitive inhibitor. Docking energy and docking affinity of callophysin A towards 3CLpro was − 8.776 kcal mol−1 and 2.73 × 106 M−1, respectively. Molecular dynamics simulation confirmed the stability of the 3CLpro-callophysin A complex. The findings of this study may serve as the basis for further validation by in vitro and in vivo studies.

Interfacial Adhesion of Cu to Self-Assembled Monolayers on SiO2

2001 ◽  
Vol 695 ◽  
Author(s):  
G. Cui ◽  
M. Lane ◽  
K. Vijayamohanan ◽  
G. Ramanath
Keyword(s):  
Binding Energy ◽  
Photoelectron Spectroscopy ◽  
Interfacial Adhesion ◽  
Adhesion Energy ◽  
Binding Energies ◽  
Self Assembled Monolayers ◽  
Chemical Binding ◽  
Barrier Materials ◽  
Assembled Monolayers ◽  
Self Assembled

ABSTRACTAs the critical feature size in microelectronic devices continues to decrease below 100 nm, new barrier materials of > 5 nm thickness are required. Recently we have shown that self-assembled monolayers (SAMs) are attractive candidates that inhibit Cu diffusion into SiO2. For SAMs to be used as barriers in real applications, however, they must also promote adhesion at the Cu/dielectric interfaces. Here, we report preliminary quantitative measurements of interfacial adhesion energy and chemical binding energy of Cu/SiO2 interfaces treated with nitrogen-terminated SAMs. Amine-containing SAMs show a ~10% higher adhesion energy with Cu, while interfaces with Cu-pyridine bonds actually show degraded adhesion, when compared with that of the reference Cu/SiN interface. However, X-ray photoelectron spectroscopy (XPS) measurements show that Cu-pyridine and Cu-amine interactions have a factor-of-four higher binding energy than that of Cu-N bonds at Cu/SiN interfaces. The lack of correlation between adhesion and chemical binding energies is most likely due to incomplete coverage of SAMs.

The binding energies of atomic nuclei III. Nuclear forces and the ground state of oxygen 16

1959 ◽  
Vol 253 (1273) ◽  
pp. 186-198 ◽  
Keyword(s):  
Binding Energy ◽  
Electron Scattering ◽  
Ground State ◽  
Binding Energies ◽  
Wave Functions ◽  
Unperturbed System ◽  
Core Radius ◽  
Nuclear Forces ◽  
Potential Core ◽  
Atomic Nuclei

The r. m. s. radius and the binding energy of oxygen 16 are calculated for several different internueleon potentials. These potentials all fit the low-energy data for two nucleons, they have hard cores of differing radii, and they include the Gammel-Thaler potential (core radius 0·4 fermi). The calculated r. m. s. radii range from 1·5 f for a potential with core radius 0·2 f to 2·0 f for a core radius 0·6 f. The value obtained from electron scattering experiments is 2·65 f. The calculated binding energies range from 256 MeV for a core radius 0·2 f to 118 MeV for core 0·5 f. The experimental value of binding energy is 127·3 MeV. The 25% discrepancy in the calculated r. m. s. radius may be due to the limitations of harmonic oscillator wave functions used in the unperturbed system.

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