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.

Detection and characterization at nM concentration of oligomers formed by hIAPP, Aβ(1–40) and their equimolar mixture using SERS and MD simulations

2018 ◽  
Vol 20 (31) ◽  
pp. 20588-20596 ◽  
Author(s):  
Luisa D’Urso ◽  
Marcello Condorelli ◽  
Orazio Puglisi ◽  
Carmelo Tempra ◽  
Fabio Lolicato ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Structural Investigation ◽  
Md Simulations ◽  
Equimolar Mixture ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations

We report a structural investigation on IAPP, Aβ(1–40) and their equimolar mixture at nM concentration using SERS spectroscopy and molecular dynamic simulations.

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 Identification of the Interactions Interference Between the PH and START Domain of CERT by Limonoid and HPA Inhibitors

2020 ◽  
Vol 7 ◽  
Author(s):  
Mariem Ghoula ◽  
Axelle Le Marec ◽  
Christophe Magnan ◽  
Hervé Le Stunff ◽  
Olivier Taboureau
Keyword(s):  
Molecular Dynamic ◽  
Binding Affinity ◽  
Computational Study ◽  
Md Simulations ◽  
Sphingolipid Metabolism ◽  
Molecular Dynamic Simulations ◽  
Ph Domain ◽  
Dynamic Simulations ◽  
The Difference ◽  
The Stability

The multi domain ceramide transfer protein (CERT) which contains the domains START and PH, is a protein that allows the transport of ceramide from the endoplasmic reticulum to the Golgi and so it plays a major role in sphingolipid metabolism. Recently, the crystal structure of the PH-START complex has been released, suggesting an inhibitory action of START to the binding of the PH domain to the Golgi apparatus and thus limiting the CERT activity. Our study presents a combination of docking and molecular dynamic simulations of N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamides (HPA) analogs and limonoids compounds known to inhibit CERT. Through our computational study, we compared the binding affinity of 14 ligands at both domains (START and PH) and also at the START-PH interface, including several mutations known to play a role in the CERT’s activity. At the difference of HPA compounds, limonoids have a stronger binding affinity for the START-PH interface. Furthermore, 2 inhibitors (HPA-12 and isogedunin) were investigated through molecular dynamic (MD) simulations. 50 ns of molecular dynamic simulations have displayed the stability of isogedunin as well as keys residues in the binding of this molecule at the interface of the PH-START complex. Therefore, this study suggests a novel inhibitory mechanism of CERT for limonoid compounds involving the stabilization of the START-PH interface. This could help to develop new and potentially more selective inhibitors of this transporter, which is a potent target in cancer therapy.

Studies on the bioactivities and molecular mechanism of antioxidant peptides by 3D-QSAR, in vitro evaluation and molecular dynamic simulations

2020 ◽  
Vol 11 (4) ◽  
pp. 3043-3052 ◽  
Author(s):  
Wenli Yan ◽  
Guimei Lin ◽  
Rong Zhang ◽  
Zhen Liang ◽  
Wenjuan Wu
Keyword(s):  
Molecular Dynamic ◽  
Molecular Mechanism ◽  
3D Qsar ◽  
Md Simulations ◽  
Molecular Dynamic Simulations ◽  
Antioxidant Peptides ◽  
Dynamic Simulations ◽  
In Vitro Evaluation

The bioactivities and molecular mechanism of two novel antioxidant peptides were investigated by 3D-QSAR, in vitro evaluation and MD simulations.

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

Molecular dynamic simulations on the interaction between an HTPE polymer and energetic plasticizers in a solid propellant

RSC Advances ◽  
2015 ◽  
Vol 5 (65) ◽  
pp. 52844-52851 ◽  
Author(s):  
Xiao-long Fu ◽  
Xue-zhong Fan ◽  
Xue-hai Ju ◽  
Xiao-fei Qi ◽  
JI-zhen Li ◽  
...  
Keyword(s):  
Mechanical Property ◽  
Molecular Dynamics ◽  
Molecular Dynamic ◽  
Solid Propellant ◽  
Md Simulations ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Energetic Plasticizers

In order to explore effects of polymer and plasticizers on miscibility and mechanical property, molecular dynamics (MD) simulations is performed to investigate the Hydroxy Terminated PolyEther (HTPE) polymer and some energetic plasticizers.

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