Homology Modeling, Docking Studies and Molecular Dynamic Simulations Using Graphical Processing Unit Architecture to Probe the Type-11 Phosphodiesterase Catalytic Site: A Computational Approach for the Rational Design of Selective Inhibitors

2013 ◽  
Vol 82 (6) ◽  
pp. 718-731 ◽  
Author(s):  
Elena Cichero ◽  
Pasqualina D'Ursi ◽  
Marco Moscatelli ◽  
Olga Bruno ◽  
Alessandro Orro ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Molecular Dynamic ◽  
Rational Design ◽  
Docking Studies ◽  
Computational Approach ◽  
Molecular Dynamic Simulations ◽  
Processing Unit ◽  
Selective Inhibitors ◽  
Dynamic Simulations ◽  
Graphical Processing

scholarly journals Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 118
Author(s):  
Siao Chen ◽  
Yi He ◽  
Yajiao Geng ◽  
Zhi Wang ◽  
Lu Han ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Md Simulations ◽  
Docking Studies ◽  
Molecular Dynamic Simulations ◽  
Terminal Protein ◽  
Dynamic Simulations ◽  
Binding Effect ◽  
Computational Alanine Scanning ◽  
Α Helix ◽  
Effect Of Inhibitors

Bromodomain and extra-terminal domain (BET) subfamily is the most studied subfamily of bromodomain-containing proteins (BCPs) family which can modulate acetylation signal transduction and produce diverse physiological functions. Thus, the BET family can be treated as an alternative strategy for targeting androgen-receptor (AR)-driven cancers. In order to explore the effect of inhibitors binding to BRD4 (the most studied member of BET family), four 150 ns molecular dynamic simulations were performed (free BRD4, Cpd4-BRD4, Cpd9-BRD4 and Cpd19-BRD4). Docking studies showed that Cpd9 and Cpd19 were located at the active pocket, as well as Cpd4. Molecular dynamics (MD) simulations indicated that only Cpd19 binding to BRD4 can induce residue Trp81-Ala89 partly become α-helix during MD simulations. MM-GBSA calculations suggested that Cpd19 had the best binding effect with BRD4 followed by Cpd4 and Cpd9. Computational alanine scanning results indicated that mutations in Phe83 made the greatest effects in Cpd9-BRD4 and Cpd19-BRD4 complexes, showing that Phe83 may play crucial roles in Cpd9 and Cpd19 binding to BRD4. Our results can provide some useful clues for further BCPs family search.

Molecular dynamic simulations of Co(III) and Ru(II) polypyridyl complexes and docking studies with dsDNA

2013 ◽  
Vol 22 (11) ◽  
pp. 5557-5565 ◽  
Author(s):  
Navaneetha Nambigari ◽  
Ramasree Dulapalli ◽  
Kiran Kumar Mustyala ◽  
Vasavi Malkhed ◽  
Uma Vuruputuri ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Docking Studies ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Polypyridyl Complexes

scholarly journals Evolution of the Computational Pharmaceutics Approaches in the Modeling and Prediction of Drug Payload in Lipid and Polymeric Nanocarriers

2021 ◽  
Vol 14 (7) ◽  
pp. 645
Author(s):  
Shaymaa A. Abd-algaleel ◽  
Hend M. Abdel-Bar ◽  
Abdelkader A. Metwally ◽  
Rania M. Hathout
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Molecular Dynamic ◽  
Docking Studies ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Polymeric Nanocarriers ◽  
Modeling And Prediction ◽  
Wet Lab ◽  
Key Aspects

This review describes different trials to model and predict drug payload in lipid and polymeric nanocarriers. It traces the evolution of the field from the earliest attempts when numerous solubility and Flory-Huggins models were applied, to the emergence of molecular dynamic simulations and docking studies, until the exciting practically successful era of artificial intelligence and machine learning. Going through matching and poorly matching studies with the wet lab-dry lab results, many key aspects were reviewed and addressed in the form of sequential examples that highlighted both cases.

scholarly journals Docking Studies and Molecular Dynamic Simulations Reveal Different Features of IDO1 Structure

2016 ◽  
Vol 35 (8-9) ◽  
pp. 449-459 ◽  
Author(s):  
Francesco Antonio Greco ◽  
Answald Bournique ◽  
Alice Coletti ◽  
Chiara Custodi ◽  
Daniela Dolciami ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Docking Studies ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations

scholarly journals Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE

2021 ◽  
Vol 22 (17) ◽  
pp. 9447
Author(s):  
Pratibha Magar ◽  
Oscar Parravicini ◽  
Šárka Štěpánková ◽  
Katarina Svrčková ◽  
Adriana D. Garro ◽  
...  
Keyword(s):  
Quantum Theory ◽  
Molecular Modeling ◽  
Molecular Dynamic ◽  
Active Site ◽  
Inhibitory Activity ◽  
Selectivity Index ◽  
Molecular Dynamic Simulations ◽  
Selective Inhibitors ◽  
Dynamic Simulations

A series of 14 target benzyl [2-(arylsulfamoyl)-1-substituted-ethyl]carbamates was prepared by multi-step synthesis and characterized. All the final compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and the selectivity index (SI) was determined. Except for three compounds, all compounds showed strong preferential inhibition of BChE, and nine compounds were even more active than the clinically used rivastigmine. Benzyl {(2S)-1-[(2-methoxybenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5k), benzyl {(2S)-1-[(4-chlorobenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5j), and benzyl [(2S)-1-(benzylsulfamoyl)-4-methylpentan-2-yl]carbamate (5c) showed the highest BChE inhibition (IC50 = 4.33, 6.57, and 8.52 µM, respectively), indicating that derivatives 5c and 5j had approximately 5-fold higher inhibitory activity against BChE than rivastigmine, and 5k was even 9-fold more effective than rivastigmine. In addition, the selectivity index of 5c and 5j was approx. 10 and that of 5k was even 34. The process of carbamylation and reactivation of BChE was studied for the most active derivatives 5k, 5j. The detailed information about the mode of binding of these compounds to the active site of both BChE and AChE was obtained in a molecular modeling study. In this study, combined techniques (docking, molecular dynamic simulations, and QTAIM (quantum theory of atoms in molecules) calculations) were employed.

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