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doi:10.1002/jcc.v30:16

Cited by 80 publications

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“…To investigate the role of electrostatics in protein-protein association, the electrostatic component of the binding free energy needs to be accurately calculated. However, there are three major obstacles in in silico modeling of the binding free energy of biological macromolecules: (1) the binding occurs in a water phase consisting of millions of water molecules whose positions and orientations vary dynamically [17][18][19]; (2) the unbound and bound monomers are also dynamical structures existing as an ensemble of structures, and these ensembles could be quite different for unbound versus bound monomers [20][21][22][23][24][25], and (3) the charged states of the ionizable groups may be nonstandard in the unbound and bound monomers and even may change due to the binding [26][27][28][29][30]. Taking the above effects rigorously into account in the computational protocol is a challenge.…”

Section: Modeling the Electrostatic Component Of The Binding Free Energymentioning

confidence: 99%

On the role of electrostatics in protein–protein interactions

Witham²,

2011

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The role of electrostatics on protein-protein interactions and binding is reviewed in this article. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and basic electrostatic effects occurring upon the formation of the complex are discussed. The role of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated and indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartment. At the end, the similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity.

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Section: Modeling the Electrostatic Component Of The Binding Free Energymentioning

confidence: 99%

On the role of electrostatics in protein–protein interactions

Witham²,

2011

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“…The binding mode of ChalcEA on the antagonist-form of hERα42 was predicted using AutoDock 4.2 43. Initially, the co-crystallized ligand, 4-OHT, was re-docked into the ligand-binding site of hERα, resulted in a docking score (free energy of binding) of −9.7 kcal/mol.…”

Section: Resultsmentioning

confidence: 99%

<p>Cytotoxicity Of Chalcone Of <em>Eugenia aquea</em> Burm F. Leaves Against T47D Breast Cancer Cell Lines And Its Prediction As An Estrogen Receptor Antagonist Based On Pharmacophore-Molecular Dynamics Simulation</p>

Muchtaridi

Syahidah

Subarnas

et al. 2019

AABC

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BackgroundThe 2ʹ,4ʹ-dihydroxy-6-methoxy-3,5-3-dimethylchalcone (ChalcEA) isolated from Eugenia aquea Burm f. leaves has potential anticancer activity against human breast-adenocarcinoma cell lines (MCF-7) with an IC50 value of 250 µM. However, its apoptotic activity on the T47D breast cancer cell lines which is involving caspase-3 has not been investigated.Materials and methodsTherefore, this study aims to evaluate the cytotoxicity of ChalcEA on the T47D cell lines using the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST) method and to predict its possible antagonistic activity on the human estrogen receptor alpha (hERα) using pharmacophore and molecular dynamics (MD) methods. The in vitro test of 10 synthesized ChalcEA derivatives was also performed as an insight into the further development of its structure as an anticancer agent.ResultsIt is shown that ChalcEA has an IC50 of 142.58 ± 4.6 µM against the hERα-overexpressed T47D breast cancer cell lines, indicating its possible mechanism of anticancer activity as an antagonist of hERα. Pharmacophore study showed that ChalcEA shares similar features with the known hERα antagonist, 4-hydroxytamoxifen (4-OHT), which has hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), ring aromaticity (RA), and hydrophobicity (Hy) features. Molecular docking showed that ChalcEA formed hydrogen bonds with Glu353 and Arg394, and hydrophobic interactions in a similar manner with 4-OHT. Moreover, MD simulations showed that ChalcEA destabilized the conformation of His524, a remarkable behavior of a known hERa antagonist, including 4-OHT. Furthermore, the 10 best chalcone derivatives resulted from pharmacophore- and docking-based screening, were tested against the T47D cell lines. None of the derivatives have better activity than ChalcEA. It is suggested that the functional groups at the B-ring of ChalcEA are interesting to be further optimized in the next studies.ConclusionChalcEA might act as an antagonist toward hERα, thus warranting further investigation as a potential anticancer agent.

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Juvenile Hormone Epoxide Hydrolase: a Promising Target for Hemipteran Pest Management

Tusun

Liang

et al. 2017

Sci Rep

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Juvenile hormone epoxide hydrolase (JHEH) has attracted great interest because of its critical role in the regulation of juvenile hormone (JH) in insects. In this study, one JHEH gene from Apolygus lucorum (AlucJHEH) was characterized in terms of deduced amino acid sequence, phylogeny, homology modeling and docking simulation. The results reveals a conserved catalytic mechanism of AlucJHEH toward JH. Our study also demonstrates that the mRNA of AlucJHEH gene was detectable in head, thorax and abdomen from all life stages. To functionally characterize the AlucJHEH gene, three fragments of double-stranded RNAs (dsRNAs) were designed to target different regions of the sequence. Injection of 3rd nymphs with dsRNA fragments successfully knocked down the target gene expression, and a significantly decreased survival rate was observed, together with a molting block, These findings confirm the important regulatory roles of AlucJHEH in A. lucorum and indicate this gene as a promising target for future hemipterans pest control.

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Cited by 80 publications

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On the role of electrostatics in protein–protein interactions

On the role of electrostatics in protein–protein interactions

<p>Cytotoxicity Of Chalcone Of <em>Eugenia aquea</em> Burm F. Leaves Against T47D Breast Cancer Cell Lines And Its Prediction As An Estrogen Receptor Antagonist Based On Pharmacophore-Molecular Dynamics Simulation</p>

Juvenile Hormone Epoxide Hydrolase: a Promising Target for Hemipteran Pest Management

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