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Occupancy map of compounds in protein compound system. A) The occupancy map of kanamycin on the surface of protein (green) in shown in blue. B) The occupancy map of kanamycin on the surface of protein (green) in shown in blue and streptomycin in red. https://doi.org/10.1371/journal.pone.0288264.g002
Source publication
Coarse-grained simulations have emerged as a valuable tool in the study of large and complex biomolecular systems. These simulations, which use simplified models to represent complex biomolecules, reduce the computational cost of simulations and enable the study of larger systems for longer periods of time than traditional atomistic simulations. GR...
Contexts in source publication
Context 1
... plot can be seen in Fig 2A with the protein shown in green colored surface representation and the occupancy of kanamycin shown in blue mesh representation. ...
Context 2
... the above-mentioned protocol, we run CG simulations for 2 microseconds (μs), we identify the binding and retention ability of the compounds within the binding pocket. Occupancy map is shown in Fig 2B, the protein shown in green colored surface representation and the occupancy of kanamycin shown in blue mesh representation and streptomycin in red mesh representation. The results show the competitive ability of the compounds to interact with the binding pocket and over lapping with each other, which corresponds to the ability of the protein to bind to both the aminoglycosides. ...
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Citations
... The simulation of TLR-adjuvant complexes was performed using the GROMOS96 force field parameters. [19] The introduction of Na+ and Cl − ions was employed to neutralize charges within the complexes. Simulations of water molecules utilized the simple point-charged water model. ...
Background
The imperative need for effective vaccines against viral diseases has intensified research on adjuvants to enhance immune responses. Toll-like receptor (TLR) agonists, such as Imiquimod, Resiquimod, and CpG oligodeoxynucleotides (CpG ODN), are some crucial components in vaccine formulations. This study investigated the molecular interactions and binding affinities of TLR4, TLR7/8, and TLR9 agonists, through in silico techniques.
Methods
The three-dimensional structure of human TLR9 was predicted using Iterative Threading ASSEmbly Refinement. Homology modeling was employed using a multi-step approach to generate the human TLR9 model including template identification, ab initio modeling, iterative refinement, and final model generation of the crystallographic structure. Molecular docking and simulation studies were performed using AutoDock Vina, HDOCK, and GROningen MAchine for Chemical Simulations tools. The molecular docking study revealed binding sites and binding affinities of adjuvants in the binding regions of target TLRs. Molecular dynamics simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area calculations ascertain the stability and binding energies of the TLR-adjuvant complexes.
Results
Results indicate distinct interactions, with Resiquimod showing superior affinity toward TLR7. QS21, on the other hand, emerged as a potent TLR4 agonist, while CpG ODN 2006 binds specifically to TLR9. The study proposes a strategic combination of QS21, Resiquimod, and CpG ODN 2006 as a potential adjuvant system, offering a multifaceted approach to enhance vaccine efficacy.
Conclusions
This study furnishes preliminary data and establishes the foundational framework for subsequent inquiries encompassing both in vitro and in vivo studies concerning vaccine adjuvant systems.
Elucidating the intricate interplay between enzymes and natural compounds is essential for designing therapeutic strategies. This study employs advanced computational techniques to explore the binding mechanisms between quercetin 2,3-dioxygenase (QDO) and oroxylin A, revealing specific interaction patterns and key residues crucial to the formation of the QDO-oroxylin A complex. Molecular docking simulations revealed a favorable binding affinity (docking score: -5.6 kcal/mol) between Oroxylin A and the active site cavity of QDO, which was supported by Oroxylin A's specific orientation (Pose 3). Despite an observed RMSD value of 2.776 indicating a moderate deviation between the docked pose and the reference structure, the formation of two hydrogen bonds with GLN 93 chain D underscores specific molecular interactions driving the binding process. This hydrogen bond formation suggested the presence of a stable and specific binding mode between Oroxylin A and QDO, likely influencing the functional dynamics of the enzyme, necessitating further refinement and validation of the docking model. The ensuing deliberation on the implications of Oroxylin A include its potential as a modulator of QDO activity, emphasizing the importance of molecular-level insights in comprehending enzyme-compound interactions. Oroxylin A, a quercetin 2,3-dioxygenase inhibitor, was used in combination with other agents to prolong the biological impacts of quercetin, thereby amplifying its antioxidant and anti-inflammatory effects. This strategic approach exhibits promise in augmenting cardioprotective benefits, immune system support, and protection against diverse pathological conditions. Subsequent considerations of dosage, bioavailability, and healthcare professional consultation are imperative for judicious supplementation, particularly in individuals with prevailing health conditions or medications. This ongoing in silico study is dedicated to revealing the potential synergistic interactions of Oroxylin A, potentiating the long-term effects of quercetin and advancing our understanding of these intricacies.
Amaç: Prostat kanseri (PC), dünya çapında erkeklerde kanserden ölümlerin en yaygın nedenlerinden biridir ve PC'yi tedavi etmek için yeni ilaçlar halen geliştirilmektedir. Şırınga asidi (SA), çeşitli tümörlerde antiinflamatuar ve metabolik düzenleyici etkiler ve antitümör aktiviteleri sergileyen bir polifenolik bileşiktir. Bu çalışma, SA'nın DU-145 hücreleri üzerindeki antiproliferatif ve antitümör aktivitelerini araştırmayı amaçladı. Yöntemler: SA'nın antiproliferatif etkisini belirlemek için MTT, antioksidan-oksidan etkilerini belirlemek için SOD-MDA analizleri kullanıldı. Bulgular: SA, in vitro olarak DU-145 hücre proliferasyonunu önemli ölçüde baskıladı. Ayrıca SOD düzeylerini düşürürken, MDA düzeylerinde ise ciddi bir artışa neden olmuştur. Sonuç: Bulgularımız SA'nın iyileştirici etkisini hedef alarak PC'nin antitümör potansiyelini ortaya çıkardı. Anahtar Kelimeler: DU-145, MDA, Prostat kanseri, SOD, Şırınga asidi
