scholarly journals Dynamic Coupling of Tyrosine 185 with the Bacteriorhodopsin Photocycle, as Revealed by Chemical Shifts, Assisted AF-QM/MM Calculations and Molecular Dynamic Simulations

2021 ◽  
Vol 22 (24) ◽  
pp. 13587
Author(s):  
Sijin Chen ◽  
Xiaoyan Ding ◽  
Chao Sun ◽  
Anthony Watts ◽  
Xiao He ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Molecular Mechanism ◽  
Chemical Shifts ◽  
Proton Translocation ◽  
Md Simulations ◽  
Binding Pocket ◽  
Dynamic Coupling ◽  
Dynamic Simulations ◽  
Dynamic Regulation ◽  
Aromatic Residues

Aromatic residues are highly conserved in microbial photoreceptors and play crucial roles in the dynamic regulation of receptor functions. However, little is known about the dynamic mechanism of the functional role of those highly conserved aromatic residues during the receptor photocycle. Tyrosine 185 (Y185) is a highly conserved aromatic residue within the retinal binding pocket of bacteriorhodopsin (bR). In this study, we explored the molecular mechanism of the dynamic coupling of Y185 with the bR photocycle by automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) calculations and molecular dynamic (MD) simulations based on chemical shifts obtained by 2D solid-state NMR correlation experiments. We observed that Y185 plays a significant role in regulating the retinal cis–trans thermal equilibrium, stabilizing the pentagonal H-bond network, participating in the orientation switch of Schiff Base (SB) nitrogen, and opening the F42 gate by interacting with the retinal and several key residues along the proton translocation channel. Our findings provide a detailed molecular mechanism of the dynamic couplings of Y185 and the bR photocycle from a structural perspective. The method used in this paper may be applied to the study of other microbial photoreceptors.

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.

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 Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction: an in silico study

2021 ◽  
Author(s):  
Chiara Luise ◽  
Dina Robaa ◽  
Wolfgang Sippl
Keyword(s):  
Molecular Dynamic ◽  
In Silico ◽  
Binding Pocket ◽  
Binding Mode ◽  
Molecular Dynamic Simulations ◽  
Flexible Docking ◽  
Dynamic Simulations ◽  
Binding Mode Prediction ◽  
Aromatic Cage ◽  
The Right

AbstractSome of the main challenges faced in drug discovery are pocket flexibility and binding mode prediction. In this work, we explored the aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction by means of in silico approaches. We first investigated the Spindlin1 aromatic cage plasticity by analyzing the available crystal structures and through molecular dynamic simulations. Then we assessed the ability of rigid docking and flexible docking to rightly reproduce the binding mode of a known ligand into Spindlin1, as an example of a reader protein displaying flexibility in the binding pocket. The ability of induced fit docking was further probed to test if the right ligand binding mode could be obtained through flexible docking regardless of the initial protein conformation. Finally, the stability of generated docking poses was verified by molecular dynamic simulations. Accurate binding mode prediction was obtained showing that the herein reported approach is a highly promising combination of in silico methods able to rightly predict the binding mode of small molecule ligands in flexible binding pockets, such as those observed in some reader proteins.

scholarly journals Investigations on Forming Ether Coated Iron Nanoparticle Materials by First-Principle Calculations and Molecular Dynamic Simulations

Coatings ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 395 ◽  
Author(s):  
Junlei Sun ◽  
Shixuan Hui ◽  
Pingan Liu ◽  
Ruochen Sun ◽  
Mengjun Wang
Keyword(s):  
Molecular Dynamic ◽  
Md Simulations ◽  
First Principle ◽  
Sphere Model ◽  
Dynamic Simulations ◽  
First Principle Calculations ◽  
Binding Force ◽  
Adsorption Behaviors ◽  
Single Sphere ◽  
To Come

The mechanism of coating effects between ether molecules and iron (Fe) nanoparticles was generally estimated using first-principle calculations and molecular dynamic (MD) simulations coupling with Fe (110) crystal layers and sphere models. In the present work, the optimized adsorption site and its energy were confirmed. The single sphere model in MD simulations was studied for typical adsorption behaviors, and the double sphere model was built to be more focused on the gap impact between two particles. In those obtained results, it is demonstrated that ether molecules were prone to be adsorbed on the long bridge site of the Fe (110) crystal while comparing with other potential sites. Although the coating was not completely uniform at early stages, the formation of ether layer ended up being equilibrated finally. Accompanied with charge transfer, those coated ether molecules exerted much binding force on the shell Fe atoms. Additionally, when free ether molecules were close to the gap between two nanoparticles, they were found to come under double adsorption effects. Although this effect might not be sufficient to keep them adsorbed, the movement of these ether molecules were hindered to some extent.

scholarly journals Graphene Adhesion Mechanics on Iron Substrates: Insight from Molecular Dynamic Simulations

Crystals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 579 ◽  
Author(s):  
Wang ◽  
Jin ◽  
Yang ◽  
Zong ◽  
Peng
Keyword(s):  
Molecular Dynamic ◽  
Surface Engineering ◽  
Graphene Nanosheets ◽  
Pair Potential ◽  
Md Simulations ◽  
Adhesion Energy ◽  
Dynamic Simulations ◽  
Embedded Atom ◽  
Adhesion Mechanics ◽  
Eam Potential

The adhesion feature of graphene on metal substrates is important in graphene synthesis, transfer and applications, as well as for graphene-reinforced metal matrix composites. We investigate the adhesion energy of graphene nanosheets (GNs) on iron substrate using molecular dynamic (MD) simulations. Two Fe–C potentials are examined as Lennard–Jones (LJ) pair potential and embedded-atom method (EAM) potential. For LJ potential, the adhesion energies of monolayer GN are 0.47, 0.62, 0.70 and 0.74 J/m2 on the iron {110}, {111}, {112} and {100} surfaces, respectively, compared to the values of 26.83, 24.87, 25.13 and 25.01 J/m2 from EAM potential. When the number of GN layers increases from one to three, the adhesion energy from EAM potential increases. Such a trend is not captured by LJ potential. The iron {110} surface is the most adhesive surface for monolayer, bilayer and trilayer GNs from EAM potential. The results suggest that the LJ potential describes a weak bond of Fe–C, opposed to a hybrid chemical and strong bond from EAM potential. The average vertical distances between monolayer GN and four iron surfaces are 2.0–2.2 Å from LJ potential and 1.3–1.4 Å from EAM potential. These separations are nearly unchanged with an increasing number of layers. The ABA-stacked GN is likely to form on lower-index {110} and {100} surfaces, while the ABC-stacked GN is preferred on higher-index {111} surface. Our insights of the graphene adhesion mechanics might be beneficial in graphene growing, surface engineering and enhancement of iron using graphene sheets.

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>

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.

Pressure-induced metallization of condensed-phase RDX: molecular dynamic simulations in conjunction with MSST method

2019 ◽  
Vol 97 (4) ◽  
pp. 245-253
Author(s):  
Zi-Qiu Bai ◽  
Jing Chang ◽  
Guang-Fu Ji ◽  
Ni-Na Ge
Keyword(s):  
Electronic Properties ◽  
Molecular Dynamic ◽  
Shock Loading ◽  
Md Simulations ◽  
Impact Sensitivity ◽  
Lower Sensitivity ◽  
Dynamic Simulations ◽  
Multi Scale ◽  
Cyclotrimethylene Trinitramine ◽  
The Impact

The anisotropy of impact sensitivity and microscopic electron properties of the cyclotrimethylene trinitramine (C3H6N6O6) (RDX) under shock loading are investigated in our work. The simulation is performed using molecular dynamic (MD) simulations in conjunction with multi-scale shock technique (MSST). By calculating the microscopic electronic properties and combining the thermodynamic properties, we predict that the metallization pressure of the RDX crystal is approximately 170 GPa under shock loading, which is slightly less than the metallization pressure under hydrostatic pressure. We also found that the microscopic electronic properties are related to the impact sensitivity. When the shock loading is along the z direction, the time of the transition from the insulating state to the metallization of the RDX crystal lags behind the shock loading along the x or y direction. Therefore, we predict that the RDX crystal has a lower sensitivity when the shock loading is along the z direction.

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