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.

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.

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.

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.

Spotting Differences in Molecular Dynamic Simulations of Influenza A M2 Protein-Ligand Complexes by Varying M2 construct, Lipid Bilayer and Force Field

2019 ◽  
Author(s):  
Dimitrios Kolokouris ◽  
Iris Kalenderoglou ◽  
Panagiotis Lagarias ◽  
Antonios Kolocouris
Keyword(s):  
Molecular Dynamic ◽  
Lipid Bilayer ◽  
Influenza A ◽  
Md Simulations ◽  
Membrane Curvature ◽  
Buffer Size ◽  
M2 Protein ◽  
Dynamic Simulations ◽  
Amphipathic Helices ◽  
Drug Protein Binding

<p>We studied by molecular dynamic (MD) simulations systems including the inward<sub>closed</sub> state of influenza A M2 protein in complex with aminoadamantane drugs in membrane bilayers. We varied the M2 construct and performed MD simulations in M2TM or M2TM with amphipathic helices (M2AH). We also varied the lipid bilayer by changing either the lipid, DMPC or POPC, POPE or POPC/cholesterol (chol), or the lipids buffer size, 10x10 Å<sup>2 </sup>or 20x20 Å<sup>2</sup>. We aimed to suggest optimal system conditions for the computational description of this ion channel and related systems. Measures performed include quantities that are available experimentally and include: (a) the position of ligand, waters and chlorine anion inside the M2 pore, (b) the passage of waters from the outward Val27 gate of M2 S31N in complex with an aminoadamantane-aryl head blocker, (c) M2 orientation, (d) the AHs conformation and structure which is affected from interactions with lipids and chol and is important for membrane curvature and virus budding. In several cases we tested OPLS2005, which is routinely applied to describe drug-protein binding, and CHARMM36 which describes reliably protein conformation. We found that for the description of the ligands position inside the M2 pore, a 10x10 Å<sup>2</sup> lipids buffer in DMPC is needed when M2TM is used but 20x20 Å<sup>2</sup> lipids buffer of the softer POPC; when M2AH is used all 10x10 Å<sup>2</sup> lipid buffers with any of the tested lipids can be used. For the passage of waters at least M2AH with a 10x10 Å<sup>2</sup> lipid buffer is needed. The folding conformation of AHs which is defined from hydrogen bonding interactions with the bilayer and the complex with chol is described well with a 10x10 Å<sup>2</sup> lipids buffer and CHARMM36. </p>

scholarly journals Ranking the Efficiency of Gas Hydrate Anti-agglomerants through Molecular Dynamic Simulations

2021 ◽  
Vol 125 (5) ◽  
pp. 1487-1502
Author(s):  
Stephan Mohr ◽  
Felix Hoevelmann ◽  
Jonathan Wylde ◽  
Natascha Schelero ◽  
Juan Sarria ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Gas Hydrate ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations

Construction of a coal char model and its combustion and gasification characteristics: Molecular dynamic simulations based on ReaxFF

Fuel ◽  
2021 ◽  
Vol 300 ◽  
pp. 120972
Author(s):  
Dikun Hong ◽  
Liang Liu ◽  
Chunbo Wang ◽  
Ting Si ◽  
Xin Guo
Keyword(s):  
Molecular Dynamic ◽  
Coal Char ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations
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