scholarly journals Inhibitory Reactivity of Capsaicin with α-Amylase and α-Glucosidase Related to Antidiabetes using Molecular Docking and Quantum Calculation Methods

2018 ◽  
Vol 34 (5) ◽  
pp. 2211-2228 ◽  
Author(s):  
Kultida Thongnum ◽  
Saksit Chanthai
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Inhibition Efficiency ◽  
Binding Free Energy ◽  
Total Binding Energy ◽  
Quantum Calculation ◽  
Total Binding ◽  
Alternative Drug ◽  
Diabetes Drug

This work aims to investigate the inhibitory activity of capsaicin, which is one of capsaicinoid compounds, on these enzymes using a molecular docking and quantum calculation. Acarbose, a commercial diabetes drug, was also investigated for comparison. The docking results revealed that acarbose yields better inhibition efficiency with binding free energy (ΔGbinding) of about -8.2 to -11.9 kcal/mol, and inhibition constant (Ki) of about 0.0002 to 0.4 µM, whereas capsaicin provided the ΔGbinding of -5.8 to -6.1 kcal/mol and Ki of 23.7 to 45.9 µM. The total binding energy (ΔEbinding) between each inhibitor and amino acids in active site of enzyme obtained from quantum calculation with MP2/6-31G(d,p) level is in agreement with the ΔGbinding, i.e. the ΔEbinding of acarbose was larger negative than that of capsaicin. The amino acids interacting with inhibitor as hydrogen bond mainly contribute to the total binding energy. Nevertheless, it could be concluded that capsaicinoids have high potential to be developed as an alternative drug for diabetes disease.

scholarly journals Напівемпіричний аналіз взаємодії алкоксипохідних 1,4-бенздіазепіну з ГАМКа-рецептором на підставі даних молекулярного докінгу та фармакологічного ефекту

2018 ◽  
Author(s):  
N. Ya. Golovenko ◽  
V. I. Pavlovskiy ◽  
I. P. Valivodz ◽  
V. B. Larionov
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Condensed System ◽  
Total Binding Energy ◽  
Ortho Position ◽  
Phenyl Radical ◽  
Benzodiazepine Derivatives ◽  
Effective Doses ◽  
Gaba Receptor Complex

Introduction. Pharmacological spectrum of 1.4-benzodiazepine 3-alkoxy derivatives, in contrast to classical substances, has more prominent analgesic properties, but even among the synthesized and studied molecules there are compounds with different magnitude of this effect.The aim of the study – to evaluate the molecular docking parameters of the theoretically generated structures of 1.4-benzodiazepine alkoxy derivatives with the GABA receptor complex and to compare these data with the pharmacological activity of the synthesized compounds.The molecular docking procedure was carried out using the iGEMDOCK v2.1 program, optimized structures of already synthesized and theoretically designed molecules with differing substituents in the ortho position of the phenyl radical and the "7" position of the condensed system are generated in the Avogadro program (v 1.2.0). The average effective doses of compounds (penthylenetetrazole-induced seizures, 120 mg/kg, subcutaneously 30 min after compounds administration) were studied in white mice.The binding energy of all the generated structures is within the ranges of 81.6–96.8 kcal/mol. Virtual docking data analysis of substituted alkoxy derivatives allows identifying several binding sites inherent for 7-chloro- or 7-bromo-substituted benzodiazepine derivatives. The greatest influence on the binding of chlorine-substituted alkoxy derivatives have regions with a high polarity amino acids (16-23 D) and similar hydrophilicity and hydrophobicity. The contribution of Van der Waals and hydrogen interactions to the total binding energy is determined by the presence of halogen (chlorine or bromine). In penthylenetetrazole-induced seizures test the compounds containing the chlorophenyl substituent in the hetero ring were most active (ED50 (0.42±0.10) μmol/kg for the propyloxy derivative and (0.51±0.17) μmol/kg for the ethyloxy derivative) while for the compounds with the phenyl radical, the ED50 value were much higher (5.1±2.7) μmol/kg and (17.75±1.93) μmol/kg, respectively). The analgesic effect is mainly due to the lkoxy derivatives possibility of binding to a center containing residues of basic amino acids.

Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

scholarly journals Binary Evolution in Stellar Systems

1975 ◽  
Vol 69 ◽  
pp. 95-97
Author(s):  
R. H. Miller
Keyword(s):  
Binding Energy ◽  
Massive Star ◽  
Massive Stars ◽  
Large Fraction ◽  
Stellar Systems ◽  
Total Binding Energy ◽  
Physical Systems ◽  
Total Binding ◽  
Binary Evolution ◽  
Favor Exchange

Aarseth has shown by means of n-body calculations that, in star systems with a range of particle masses, the most massive stars quickly form a binary which soon takes up a large fraction of the total binding energy of the cluster. Similar effects appear in other kinds of physical systems as well; mesic atoms behave in much the same way. The phase volumes of two otherwise equivalent stellar systems, each dominated by a tightly bound binary, favor exchange to incorporate the more massive star in the binary by a factor equal to the cube of the ratio of masses.

NONADDITIVE EFFECTS IN H2 AND HF TETRAMERS

2004 ◽  
Vol 03 (01) ◽  
pp. 15-22 ◽  
Author(s):  
JINSHAN LI ◽  
FUQIAN JING
Keyword(s):  
Binding Energy ◽  
Interaction Energy ◽  
Minimum Point ◽  
Total Binding Energy ◽  
Interaction Energies ◽  
Body Interaction ◽  
Total Binding ◽  
Intermolecular Distances ◽  
Nonadditive Effects ◽  
Negligible Contribution

Nonadditive three- and four-body interaction energies have been calculated for HF tetramer at the MP2/aug-cc-pVTZ level and for H 2 tetramer at the MP4(SDTQ)/aug-cc-pVTZ level using the so-called fifteen-point method. Calculated results show that with intermolecular distances decreasing from 3.0 to 1.7 Å the nonadditive three- and four-body interactions may be: (a) more and more attractive; (b) more and more repulsive; or (c) extremely weak. Strangely the minimum point of nonadditive three- and four-body interaction potentials has not been found up to now. For both H 2 and HF tetramers the nonadditive four-body interaction energy makes a negligible contribution to total binding energy when intermolecular distances are compressed from 3.0 to 1.7 Å.

scholarly journals Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

2020 ◽  
Vol 14 (10) ◽  
pp. 52
Author(s):  
Usman Abdulfatai ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Docking Simulation ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

scholarly journals The Effect of Deuteration on the H2 Receptor Histamine Binding Profile: A Computational Insight into Modified Hydrogen Bonding Interactions

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6017
Author(s):  
Lucija Hok ◽  
Janez Mavri ◽  
Robert Vianello
Keyword(s):  
Hydrogen Bonding ◽  
Binding Energy ◽  
Binding Free Energy ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Computational Techniques ◽  
Aqueous Environment ◽  
Total Binding Energy ◽  
H2 Receptor ◽  
Hydrogen Bonding Interactions

We used a range of computational techniques to reveal an increased histamine affinity for its H2 receptor upon deuteration, which was interpreted through altered hydrogen bonding interactions within the receptor and the aqueous environment preceding the binding. Molecular docking identified the area between third and fifth transmembrane α-helices as the likely binding pocket for several histamine poses, with the most favorable binding energy of −7.4 kcal mol−1 closely matching the experimental value of −5.9 kcal mol−1. The subsequent molecular dynamics simulation and MM-GBSA analysis recognized Asp98 as the most dominant residue, accounting for 40% of the total binding energy, established through a persistent hydrogen bonding with the histamine −NH3+ group, the latter further held in place through the N–H∙∙∙O hydrogen bonding with Tyr250. Unlike earlier literature proposals, the important role of Thr190 is not evident in hydrogen bonds through its −OH group, but rather in the C–H∙∙∙π contacts with the imidazole ring, while its former moiety is constantly engaged in the hydrogen bonding with Asp186. Lastly, quantum-chemical calculations within the receptor cluster model and utilizing the empirical quantization of the ionizable X–H bonds (X = N, O, S), supported the deuteration-induced affinity increase, with the calculated difference in the binding free energy of −0.85 kcal mol−1, being in excellent agreement with an experimental value of −0.75 kcal mol−1, thus confirming the relevance of hydrogen bonding for the H2 receptor activation.

On the total binding energy of spherical nuclei

1977 ◽  
Vol 278 (2) ◽  
pp. 319-332 ◽  
Author(s):  
G.M. Vagradov ◽  
F.A. Gareev ◽  
J. Bang
Keyword(s):  
Binding Energy ◽  
Total Binding Energy ◽  
Total Binding ◽  
Spherical Nuclei

scholarly journals Binding properties of immunoglobulin combining sites specific for terminal or nonterminal antigenic determinants in dextran.

1975 ◽  
Vol 142 (2) ◽  
pp. 435-459 ◽  
Author(s):  
J Cisar ◽  
E A Kabat ◽  
M M Dorner ◽  
J Liao
Keyword(s):  
Binding Energy ◽  
Large Fraction ◽  
Binding Constants ◽  
Antigenic Determinants ◽  
Low Molecular Weight ◽  
Total Binding Energy ◽  
Binding Properties ◽  
Total Binding ◽  
Myeloma Proteins ◽  
Mouse Myeloma

Binding constants of the dextran-reactive BALB/c mouse IgA myeloma proteins W3129 and QUPC 52 have been determined for each member of the isomaltose series of oligosaccharides and for methyl alphaDglucoside. Protein W3129 has maximum complementarity for isomaltopentaose (IM5) deltaf degrees = 7,180 cal/mol) with 55-60% of the total binding energy directed against methylalphaDglucoside. Protein QUPC 52 gives maximum binding with isomaltohexaose (IM6) (deltaF degrees = -5,340 cal/mol) and has about 70% of its total binding energy for isomaltotriose (IM3), but at most only 5% for isomaltose (IM2) or methyl alphaDglucoside. Protein W3129 precipitates with branched dextrans high in alpha (1 yields 6) linkages and reacts with but does not precipitate a synthetic alpha (1 yields 6)-linked linear dextran. Protein QUPC 52 precipitates both branched and linear dextrans. Thus, the immunodominant group for protein W3129 is mimicked by methyl alphaDglucoside and this protein reacts exclusively at the terminal nonreducing ends of alpha (1 yields 6)-linked dextran chains. Protein QUPC 52 has an immunodominant group which is expressed by IM3 but not smaller oligosaccharides and this protein can react at nonterminal locations along alpha (1 yields 6)-linked dextran chains.Precipitation of linear dextran seems to be a valid although not quantitative assay for antidextrans with nonterminal specificity. Quantitative precipitin reactions with branched and linear dextrans suggest that alpha (1 yields 6)-specific human antidextrans are mixtures of molecules having terminal and nonterminal specificities and that the fraction of each type can vary among individuals. Rabbit antisera against IM3 or IM6 coupled to bovine serum albumin also appear to contain antibodies with nonterminal specificity for dextran chains although a large fraction has terminal specificity. Low molecular weight clinical dextran N-150N (congruent to 60,000) reacted more like linear dextran than like its parent native-branched dextran B512. This is thought to result from an abundance of nonterminal determinants in clinical dextran N-150N but a very small number of functional terminal determinants per molecule. An appreciation of terminal and nonterminal specificities and of the different immunodominant structures in isomaltosyl chains has proven to be of a great value in understanding the immunochemical reactions of dextrans. Moreover, certain previous findings with fructosan-reactive mouse myeloma proteins and human antilevans (55, 84) also suggest terminal and nonterminal specificities for levan chains.

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