scholarly journals Catalytic and Molecular Properties of Rabbit Liver Carboxylesterase Acting on 1,8-Cineole Derivatives

2012 ◽  
Vol 7 (9) ◽  
pp. 1934578X1200700
Author(s):  
María del H. Loandos ◽  
Ana C. Muro ◽  
Margarita B. Villecco ◽  
Marcelo F. Masman ◽  
Paul G.M. Luiten ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Molecular Modeling ◽  
Molecular Properties ◽  
Rabbit Liver ◽  
Enantioselective Hydrolysis ◽  
Docking Simulations ◽  
Hydrogen Bond Interactions ◽  
Molecular Dynamics Calculations ◽  
Hydrolysis Of

Rabbit liver carboxylesterase (rCE) was evaluated as the catalyst for the enantioselective hydrolysis of (±)-3-endo-acetyloxy-1,8-cineole [(±)-4], which yields (1S,3S,4R)-(+)-3-acetyloxy-1,8-cineole [(+)-4] and (1R,3R,4S)-(-)-3-hydroxy-1,8-cineole [(-)-3]. Enantioselective asymmetrization of meso-3,5-diacetoxy-1,8-cineol (5) gives (1S,3S,4R,5R)-(-)-3-acetyloxy-5-hydroxy-1,8-cineole (6), with high enantioselectivity. rCE has been chosen to perform both experiments and molecular modeling simulations. Docking simulations combined with molecular dynamics calculations were used to study rCE-catalyzed enantioselective hydrolysis of cineol derivatives. Both compounds were found to bind with their acetyl groups stabilized by hydrogen bond interactions between their oxygen atoms and Ser221.

scholarly journals Contrasting the Conformational Effects of α-O-GalNAc and α-O-Man Glycan Protein Modifications and their Impact on the Mucin-Like Region of alpha-Dystroglycan

Glycobiology ◽  
2020 ◽  
Author(s):  
Andrew Borgert ◽  
B Lachele Foley ◽  
David Live
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Solution Nmr ◽  
Threonine Residue ◽  
Hydrogen Bond Interactions ◽  
Conformational Effects ◽  
Molecular Dynamics Calculations ◽  
Alpha Dystroglycan ◽  
The Impact

Abstract We have carried out a comparative study of the conformational impact of modifications to threonine residues of either α-O-Man or α-O-GalNAc in the context of a sequence from the mucin-like region of α-dystroglycan. Both such modifications can coexist in this domain of the glycoprotein. Solution NMR experiments and molecular dynamics calculations were employed. Comparing the results for a unmodified peptide Ac- PPTTTTKKP-NH2 sequence from α-dystroglycan, and glycoconjugates with either modification on the Ts, we find that the impact of the α-O-Man modification on the peptide scaffold is quite limited, while that of the α-O-GalNAc is more profound. The results for the α-O-GalNAc glycoconjugate are consistent with what has been seen earlier in other systems. Further examination of the NMR-based structure and the MD results suggest a more extensive network of hydrogen bond interactions within the α-O-GalNAc-threonine residue than has been previously appreciated, which influence the properties of the protein backbone. The conformational effects are relevant to the mechanical properties of α-dystroglycan.

Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular modeling studies, molecular dynamics, and docking simulations

2015 ◽  
Vol 33 (10) ◽  
pp. 2161-2172 ◽  
Author(s):  
D. Méndez-Luna ◽  
M. Martínez-Archundia ◽  
Rachid C. Maroun ◽  
G. Ceballos-Reyes ◽  
M.J. Fragoso-Vázquez ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Modeling ◽  
Docking Simulations ◽  
Modeling Studies ◽  
Molecular Modeling Studies

scholarly journals New Insights Into the Structure of Hydroxylated and Alkylated Glycols: A Comparative X-ray Diffraction, Raman and Molecular Dynamics Study of Ethane-1,2-Diol, 2-Methoxyethan-1-ol and 1,2-Dimethoxy Ethane

2020 ◽  
Author(s):  
Lorenzo Gontrani ◽  
Pietro Tagliatesta ◽  
Antonio Agresti ◽  
Sara Pescetelli ◽  
Marilena Carbone
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Room Temperature ◽  
Intermolecular Hydrogen Bond ◽  
Hydroxyl Groups ◽  
Gauche Conformation ◽  
X Ray ◽  
Hydrogen Bond Interactions ◽  
Diffraction Patterns ◽  
Intramolecular Hydrogen

In this study, we report a detailed experimental and theoretical investigation of three glycols, namely ethane-1,2-diol, 2-methoxyethan-1-ol and 1,2-dimethoxy ethane. For the first time, the X-Ray spectra of the latter two liquids was measured at room temperature, and they were compared with the newly measured spectrum of ethane-1,2-diol. The experimental diffraction patterns were interpreted very satisfactorily with molecular dynamics calculations, and suggest that in liquid ethane-1,2-diol most molecules are found in gauche conformation, with intramolecular hydrogen bond between the two hydroxyl groups. Intramolecular H-bonds are established in the mono-alkylated diol, but the interaction is weaker. The EDXD study also evidences strong intermolecular hydrogen-bond interactions, with short O···O correlations in both systems, while longer methyl-methyl interactions are found in 1,2-dimethoxy ethane. X-Ray studies are complemented by micro Raman investigations at room temperature and at 80°C, that confirm the conformational analysis predicted by X-Ray experiments and simulations.

Molecular Interactions Between DNA, Cocaine and Its Metabolites

2020 ◽  
Vol 12 (3) ◽  
pp. 314-324
Author(s):  
Brunna S. M. Sousa ◽  
Igor L. P. Gonçalves ◽  
Arthur F. V. F. Reis ◽  
Abel F. G. Neto ◽  
Teodorico C. Ramalho ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
The Other ◽  
Strong Interactions ◽  
Chemical Affinity ◽  
Free Energies ◽  
Docking Simulations ◽  
Human Dna ◽  
Physical Chemical ◽  
Cocaine Metabolites ◽  
Molecular Dynamics Calculations

This present work aims to investigate the physical chemical interactions between cocaine and its metabolites with the human-DNA. The investigation was performed by molecular docking and molecular dynamics calculations, where the following cocaine metabolites were analyzed: Benzoylecgonine, Cocaethylene, Ester methylecgonine and Norcocaine. From the docking simulations we observed the hydrogen interactions most likely to occur between the drugs and DNA, whereas, through the molecular dynamics, the RMSD values were obtained and analyzed along with van der Waals, electrostatic, solvation and bind free energies between DNA and cocaine, beside its metabolites. Our results showed that the guanine in the minor groove of DNA is the nucleotide with highest chemical affinity to interact with the cocaine metabolites. On the other hand, the cocaethylene and cocaine were the drugs which presented the most stable and strong interactions with DNA, which can suggest, from molecular modeling investigations, a possible genotoxic potential of these molecules.

scholarly journals Biological Regulatory Network (BRN) Analysis and Molecular Docking Simulations to Probe the Modulation of IP3R Mediated Ca2+ Signaling in Cancer

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 34
Author(s):  
Humaira Ismatullah ◽  
Ishrat Jabeen ◽  
Muhammad Tariq Saeed
Keyword(s):  
Cell Proliferation ◽  
Hydrogen Bond ◽  
Cell Death ◽  
Molecular Docking ◽  
Cancer Progression ◽  
Regulatory Network ◽  
Hydroxyl Group ◽  
Docking Simulations ◽  
Cellular Processes ◽  
Hydrogen Bond Interactions

Inositol trisphosphate receptor (IP3R) mediated Ca+2 signaling is essential in determining the cell fate by regulating numerous cellular processes, including cell division and cell death. Despite extensive studies about the characterization of IP3R in cancer, the underlying molecular mechanism initiating the cell proliferation and apoptosis remained enigmatic. Moreover, in cancer, the modulation of IP3R in downstream signaling pathways, which control oncogenesis and cancer progression, is not well characterized. Here, we constructed a biological regulatory network (BRN), and describe the remodeling of IP3R mediated Ca2+ signaling as a central key that controls the cellular processes in cancer. Moreover, we summarize how the inhibition of IP3R affects the deregulated cell proliferation and cell death in cancer cells and results in the initiation of pro-survival responses in resistance of cell death in normal cells. Further, we also investigated the role of stereo-specificity of IP3 molecule and its analogs in binding with the IP3 receptor. Molecular docking simulations showed that the hydroxyl group at R6 position along with the phosphate group at R5 position in ‘R’ conformation is more favorable for IP3 interactions. Additionally, Arg-266 and Arg-510 showed π–π and hydrogen bond interactions and Ser-278 forms hydrogen bond interactions with the IP3 binding site. Thus, they are identified as crucial for the binding of antagonists.

scholarly journals The Oxindole Derivatives, New Promising GSK-3β Inhibitors as One of the Potential Treatments for Alzheimer’s Disease—A Molecular Dynamics Approach

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 332
Author(s):  
Przemysław Czeleń ◽  
Beata Szefler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Glycogen Synthase ◽  
Molecular Properties ◽  
Binding Potential ◽  
Significant Group ◽  
Docking Simulations ◽  
Reference Molecule ◽  
Gsk 3Β

The glycogen synthase kinase 3β (GSK-3β) is a protein kinase involved in regulating numerous physiological processes such as embryonic development, transcription, insulin action, cell division cycle and multiple neuronal functions. The overexpression of this enzyme is related to many diseases such as schizophrenia, Alzheimer’s disease, diabetes and cancer. One of the basic methods of treatment in these cases is the usage of ATP-competitive inhibitors. A significant group of such compounds are indirubin and its analogs, e.g., oxindole derivatives. The compounds considered in this work are 112 newly designed oxindole derivatives. In the first stage, such molecular properties of considered compounds as toxicity and LogP were estimated. The preliminary analysis of the binding capabilities of considered compounds towards the GSK-3β active site was conducted with the use of the docking procedure. Based on obtained molecular properties and docking simulations, a selected group of complexes that were analyzed in the molecular dynamics stage was nominated. The proposed procedure allowed for the identification of compounds such as Oxind_4_9 and Oxind_13_10, which create stable complexes with GSK-3β enzyme and are characterized by the highest values of binding affinity. The key interactions responsible for stabilization of considered ligand–protein complexes were identified, and their dynamic stability was also determined. Comparative analysis including analyzed compounds and reference molecule 3a, which is also an oxindole derivative with a confirmed inhibitory potential towards GSK3B protein, clearly indicates that the proposed compounds exhibit an analogous binding mechanism, and the obtained binding enthalpy values indicate a slightly higher binding potential than the reference molecule.

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