Investigation of the interactions between Melittin and the PLGA and PLA polymers: molecular dynamic simulation and binding free energy calculation

Asadzadeh, Homayoun; Moosavi, Ali

doi:10.1088/2053-1591/ab06d3

Cited by 22 publications

(10 citation statements)

References 71 publications

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“…In pharmaceutical industry, MD has been extensively explored for free energy calculations, thermodynamics calculations, partitioning calculations, etc., which enable accurate prediction by integration of various algorithms and MD techniques [21][22][23]. MD simulations of PLGA-based polymers have been previously conducted to study their physicochemical properties, free energy calculations, and their interaction with various drug molecules, which cannot be deciphered via experimental methods [24,25].…”

Section: Introductionmentioning

confidence: 99%

Influence of lactide vs glycolide composition of poly (lactic-co-glycolic acid) polymers on encapsulation of hydrophobic molecules: molecular dynamics and formulation studies

Dobhal

Srivastav

Dandekar

et al. 2021

J Mater Sci: Mater Med

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The work demonstrates the preparation of PLGA (PLGA 50:50, PLGA 75:25) nanoparticles, to encapsulate a hydrophobic molecule (coumarin-6), using the microreactor-based continuous process. The formulations were characterized using dynamic light scattering and transmission electron microscopy to determine their size, homogeneity, zeta potential, and surface morphology. The resulting nanoparticles were safe to the CHO cells (≈80% cell survival), at the concentration of ≤600 µg/mL and were successfully taken up by the cells, as demonstrated using confocal microscopy. Moreover, imaging flow cytometry confirmed that the nanoparticles were internalized in 73.96% of the cells. Furthermore, molecular dynamics simulation and docking studies were carried out to explore the effect of polymer chain length of PLGA and lactide vs glycolide (LA:GA) ratio on their compatibility with the coumarin-6 molecules and to study the coiling and flexibility of PLGA in the presence of coumarin-6 molecules. Flory–Huggins interaction parameter (χ) was calculated for polymer chains of varying lengths and LA:GA ratio, with respect to coumarin-6. χ parameter increased with increase in polymer chain length, which indicated superior interaction of coumarin-6 with the smaller chains. Amongst all the polymeric systems, PLGA55 exhibited the strongest interaction with coumarin-6, for all the chain lengths, possibly because of their homogeneous spatial arrangements and superior binding energy. PLGA27 showed better compatibility compared to PLGA72 and PGA, whereas PLA-based polymers exhibited the least compatibility. Analysis of the radius of gyration of the polymer chains in the polymer–coumarin-6 complexes, at the end of molecular dynamics run, exhibited that the polymer chains displayed varying coiling behavior and flexibility, depending upon the relative concentrations of the polymer and coumarin-6. Factors like intra-chain interactions, spatial arrangement, inter-chain binding energies, and polymer–coumarin-6 compatibility also influenced the coiling and flexibility of polymer chains.

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Section: Introductionmentioning

confidence: 99%

Influence of lactide vs glycolide composition of poly (lactic-co-glycolic acid) polymers on encapsulation of hydrophobic molecules: molecular dynamics and formulation studies

Dobhal

Srivastav

Dandekar

et al. 2021

J Mater Sci: Mater Med

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“…Among these available techniques, molecular dynamics and docking technique which are strong computational tools that provide valuable complementary to experiment information about the details of the atomistic interactions in biological phenomena has attracted attention recently. Up to now, various researches have been performed a lot of research regarding the molecular dynamic and docking simulation to investigate the behavior of protein, aptamer, ligands, and peptides in the atomic scale [30,31]. In 2021, He et al [32] performed molecular docking simulations for an electrochemical impedimetric sensing platform based on a peptide aptamer, and they found the binding capacity of peptide aptamers by molecular docking and demonstrated that docking was an effective tool to screen peptide aptamers for amino acid-binding capacity.…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Atomic Scale Interactions between RNA and DNA Aptamers with the TNF‐α Protein

Asadzadeh

Moosavi

Alexandrakis

et al. 2021

BioMed Research International

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Interest in the design and manufacture of RNA and DNA aptamers as apta-biosensors for the early diagnosis of blood infections and other inflammatory conditions has increased considerably in recent years. The practical utility of these aptamers depends on the detailed knowledge about the putative interactions with their target proteins. Therefore, understanding the aptamer-protein interactions at the atomic scale can offer significant insights into the optimal apta-biosensor design. In this study, we consider one RNA and one DNA aptamer that were previously used as apta-biosensors for detecting the infection biomarker protein TNF-α, as an example of a novel computational workflow for selecting the aptamer candidate with the highest binding strength to a target. We combine information from the binding free energy calculations, molecular docking, and molecular dynamics simulations to investigate the interactions of both aptamers with TNF-α. The results reveal that the RNA aptamer has a more stable structure relative to the DNA aptamer. Interaction of aptamers with TNF-α does not have any negative effect on its structure. The results of molecular docking and molecular dynamics simulations suggest that the RNA aptamer has a stronger interaction with the protein. Also, these findings illustrate that basic residues of TNF-α establish more atomic contacts with the aptamers compared to acidic or pH-neutral ones. Furthermore, binding energy calculations show that the interaction of the RNA aptamer with TNF-α is thermodynamically more favorable. In total, the findings of this study indicate that the RNA aptamer is a more suitable candidate for using as an apta-biosensor of TNF-α and, therefore, of greater potential use for the diagnosis of blood infections. Also, this study provides more information about aptamer-protein interactions and increases our understanding of this phenomenon.

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“…On the basis of the properties of the PLA-HA copolymer, we inferred how melittin and doxorubicin were loaded in a polymersome. H. Asadzadeh et al confirmed the dynamics of melittin and its interactions with diverse polymers through molecular dynamics (MD) simulation [ 26 ]. Initially, polymers interact with one another, aggregate, and come in contact with melittin.…”

Section: Discussionmentioning

confidence: 99%

Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance

et al. 2023

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Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.

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Investigation of the interactions between Melittin and the PLGA and PLA polymers: molecular dynamic simulation and binding free energy calculation

Cited by 22 publications

References 71 publications

Influence of lactide vs glycolide composition of poly (lactic-co-glycolic acid) polymers on encapsulation of hydrophobic molecules: molecular dynamics and formulation studies

Influence of lactide vs glycolide composition of poly (lactic-co-glycolic acid) polymers on encapsulation of hydrophobic molecules: molecular dynamics and formulation studies

[Retracted] Atomic Scale Interactions between RNA and DNA Aptamers with the TNF‐α Protein

Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance

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