CHARMM-GUI Synthetic Polymer Modeler for Modeling and Simulation of Synthetic Polymers

Choi, Yeol Kyo; Duran, Tibo; Im, Wonpil

doi:10.1016/j.bpj.2018.11.3074

Cited by 2 publications

(1 citation statement)

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“…Figure a shows the AA structure of a block copolymer PEG (45 monomers)–PLA (24 monomers) based on the molecular weight of PEG (2kD)–PLA (1.7kD) used in experimental work . The AA polymer chain was built using CHARMM , and CHARMM-GUI () − as an atactic structure, similar to the materials used in the experimental studies. CHARMM force field was used to parameterize and model the ethylene glycol and lactic acid monomers.…”

Section: Computational Models and Methodsmentioning

confidence: 99%

Coarse-Grained Molecular Dynamics Simulations of Paclitaxel-Loaded Polymeric Micelles

et al. 2022

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A continuous manufacturing technology based on coaxial turbulent jet in coflow was previously developed to produce paclitaxel-loaded polymeric micelles. Herein, coarse-grained molecular dynamics (CG-MD) simulations were implemented to better understand the effect of the material attributes (i.e., the drug−polymer ratio and the ethanol concentration) and process parameters (i.e., temperature) on the self-assembly process of polymeric micelles as well as to provide molecular details on micelle instability. An all-atom (AA) poly (ethylene glycol)-poly (lactic acid) (PEG−PLA) polymer model was developed as the reference for parameterizing a coarse-grained (CG) model, and the AA polymer model was further validated with experimental glass transition temperature (T g ). The model transferability was verified by comparing structural properties between the AA and CG models. The CG model was further validated with experimental data, including micelle particle size measurements and drug encapsulation efficiency. Furthermore, the encapsulation of paclitaxel into the polymeric micelles was included in the simulations, taking into consideration the interactions between the paclitaxel and the polymers. The results from various points of view demonstrated a strong dependence of the shape of the micelles on the drug encapsulation, with micelles transitioning from spherical to ellipsoidal structures with an increasing paclitaxel amount. Simulation data were also used to identify the critical aggregation number (i.e., the number of polymer and drug molecules required for transition from one shape to another). Improved micellar structural stability was found with a larger micellar size and less solvent accessibility. Lastly, an evaluation was performed on the micellar dissociation free energy using a steered molecular dynamics simulation over a range of temperatures and ethanol concentrations. These simulations revealed that at higher ethanol and temperature conditions, micelles become destabilized, resulting in greater paclitaxel release. The increased drug release was determined to originate from the solvation of the hydrophobic core, which promoted micellar swelling and an associated reduction in hydrophobic interactions, leading to a loosely packed micellar structure.

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Section: Computational Models and Methodsmentioning

confidence: 99%

Coarse-Grained Molecular Dynamics Simulations of Paclitaxel-Loaded Polymeric Micelles

et al. 2022

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Molecular Simulation Study on the Interaction between Tyrosinase and Flavonoids from Sea Buckthorn

Guo

Lian

et al. 2021

ACS Omega

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Isorhamnetin, kaempferol, myricetin, and quercetin are four kinds of secondary metabolites in sea buckthorn, which have a wide range of biological activities. Investigating their interactions with tyrosinase at the atomic level can improve the bioavailability of sea buckthorn. Both molecular docking and molecular dynamics simulation methods were employed to study the interactions of these ligands with tyrosinase. The results of molecular docking indicated that these four small molecules such as isorhamnetin, kaempferol, myricetin, and quercetin can all dock into the active center of tyrosinase, and by occupying the active site, they can prevent substrate binding, thereby reducing the catalytic activity of tyrosinase. Molecular dynamics simulation trajectory analysis showed that all tyrosinase–ligand complexes reach an equilibrium within 100 ns. In addition, quercetin has the lowest binding energy among these four ligands, and the complex with tyrosinase is the most stable. This study not only provides valuable information for improving the bioavailability of sea buckthorn but also contributes to the discovery of effective natural inhibitors of tyrosinase.

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CHARMM-GUI Synthetic Polymer Modeler for Modeling and Simulation of Synthetic Polymers

Cited by 2 publications

References 0 publications

Coarse-Grained Molecular Dynamics Simulations of Paclitaxel-Loaded Polymeric Micelles

Coarse-Grained Molecular Dynamics Simulations of Paclitaxel-Loaded Polymeric Micelles

Molecular Simulation Study on the Interaction between Tyrosinase and Flavonoids from Sea Buckthorn

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