1,720,966 research outputs found
Interaction of Curcumin with PEO–PPO–PEO Block Copolymers: A Molecular Dynamics Study
No full textCurcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood. In this paper, we propose a molecular dynamics simulation study of the interaction of Curcumin with block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted considering the smallest PEO and PPO oligomers and multiple chains of the block copolymer Pluronic P85. Our study shows that the more hydrophobic 1,2-dimethoxypropane (DMP) molecules and PPO block preferentially coat the Curcumin molecule. In the case of the Pluronic P85, simulation shows formation of a drug–polymer aggregate within 50 ns. This process leaves exposed the PEO part of the polymers, resulting in better solvation and stability of the drug in water
Molecular basis of substrate translocation through the outer membrane channel OprD of Pseudomonas aeruginosa
No full textThe objective of this study is to identify the structural features governing the transport of molecules through nanometric channel proteins at a molecular level. Our focus is to come up with a precise understanding of the structure and dynamics of the outer membrane porin OprD of the Gram-negative bacterium Pseudomonas aeruginosa by studying the translocation of natural amino acid residues/ substrates through it. We used in silico electrophysiology and metadynamics simulation techniques as they can provide precise information on the molecule/channel interactions at the atomic scale that allows testing quantitative structure–function relationships. We performed our simulations on the whole OprD protein, with all loops modelled and without any constraints to keep the channel open. Dynamics of both internal and external loops and the polar nature of the eyelet region play important roles in modulating the translocation of molecules through OprD by creating two alternative paths for transloca- tion. All positive residues take the main path upon binding in the negative pocket just above the constric- tion region. The same factor is unfavourable for negative substrates and hence they have a relatively high barrier for translocation. Differently, neutral substrates do not show any specificity and they can follow the two alternative paths
Diffusion of 1,2-Dimethoxyethane and 1,2-Dimethoxypropane through Phosphatidycholine Bilayers: A Molecular Dynamics Study
No full textIn this paper, a theoretical study of 1,2-dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP) at water/n-heptane and 1,2-dimyristoyl-sn-glycero-3-phospatidycholine (DMPC) lipid bilayer/water interfaces using the umbrella sampling method is reported. Recently proposed GROMOS96/OPLS compatible models for DME and DMP have been used for the simulation studies. The percolation free energy barrier of one DME and DMP molecule from water to n-heptane phase calculated using the umbrella sampling method turned out to be equal to ∼18.5 kJ/mol and ∼6 kJ/mol, respectively. In the case of the DMPC lipid bilayer, overall free energy barriers of ∼20 kJ/mol and ∼12 kJ/mol were obtained for DME and DMP, respectively. The spontaneous diffusion of DME and DMP in the lipid bilayer has also been investigated using unconstrained molecular dynamics simulations at the water/DMPC interface and inside the lipid bilayer. As expected from the estimated percolation barriers, simulation results show that DME, contrary to DMP, spontaneously diffuse into the aqueous solution from the lipid interior. In addition, simulations with multiple DME or DMP molecules at the interface show spontaneous diffusion within 50 ns inside the DMPC layer only for DMP
Structure and dynamics of 1,2-dimethoxyethane and 1,2-dimethoxypropane in aqueous and non-aqueous solutions: A molecular dynamics study
No full textHerein, we report a comparative modelling study of 1,2-dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP) at 298 K and 318 K in the liquid state, water mixtures, and at infinite dilution condition in water, methanol, carbon tetrachloride, and n-heptane. Both DME and DMP are united-atom models compatible with GROMOS/OPLS force fields. Calculated thermodynamic and structural properties of the pure DME and DMP liquids resulted in excellent agreement with the experimental data. In aqueous solutions, densities, diffusion coefficients, and concentration dependent conformers of DME, were in agreement with experimental data. The calculated free energy of solvation (ΔGhyd) at 298 K is equal to –22.1 ± 0.8 kJ mol−1 in good agreement with the experimental value of 20.2 kJ mol−1. In addition, the free energy of solvation of DME in non-aqueous solvents follows the trend methanol ≈ water < carbon tetrachloride < n-heptane, consistently with the dielectric constant of the solvents. On contrary, the presence of an extra methyl group on chiralcarbon makes DMP less soluble than DME in water (ΔGhyd = −16.0 ± 1.1 kJ mol−1) but more soluble in non-polar solvents as n-heptane. Finally, for the DMP the chiral discrimination of the two enantiomers was calculated as solvation free energy difference of one DMP isomer in the solution of the other. The obtained value of ΔΔGRS = –3.7 ± 1.4 kJ mol−1 indicates a net chiral discrimination of the two enantiomers
Molecular dynamics simulation study of solvent effects on conformation and dynamics of polyethylene oxide and polypropylene oxide chains in water and in common organic solvents
No full textIn this paper, the conformation and dynamics properties of polyethylene oxide (PEO) and polypropylene oxide (PPO) polymer chains at 298 K have been studied in the melt and at infinite dilution condition in water, methanol, chloroform, carbon tetrachloride, and n-heptane using molecular dynamics simulations. The calculated density of PEO melt with chain lengths of n = 2, 3, 4, 5 and, for PPO, n = 7 are in good agreement with the available experimental data. The conformational properties of PEO and PPO show an increasing gauche preference for the O–C–C–O dihedral in the following order water>methanol>chloroform>carbon tetrachloride = n-heptane. On the contrary, the preference for trans conformation has a maximum in carbon tetrachloride and n-heptane followed in the order by chloroform, methanol, and water. The PEO conformational preferences are in qualitative agreement with results of NMR studies. PEO chains formed different types of hydrogen bonds with polar solvent molecules. In particular, the occurrence of bifurcated hydrogen bonding in chloroform was also observed. Radii of gyration of PEO chains of length larger than n = 9 monomers showed a good agreement with light scattering data in water and in methanol. For the shorter chains the observed deviations are probably due to the enhanced hydrophobic effects caused by the terminal methyl groups. For PEO the fitting of end-to-end distance distributions with the semi-flexible chain model at 298 K provided persistence lengths of 0.375 and 0.387 nm in water and methanol, respectively. Finally, the radius of gyration of Pluronic P85 turned out to be 2.25 ± 0.4 nm at 293 K in water in agreement with experimental data
Theoretical Study of the Interaction of Amphiphilic Block Co-polymers with Biological Interfaces and Small Molecules
No full textSynthetic polymers are versatile materials with an extraordinary range of technological applications playing essential and ubiquitous roles in everyday life. Presently, the applications of polymers are not limited to traditional areas of technology but extend to novel uses in the areas of nanotechnology connected to medicine and pharmacology. Polyethylene oxide (PEO) and polypropylene oxide (PPO) homo-polymers as well as the block co-polymers based on them (Pluronics or Poloxamers) are among the most versatile polymers used in these fields. These polymers have the advantages of being non-toxic, easily available, economic and customizable to meet specific purposes. Despite many experimental and theoretical studies on them, the actual mechanisms of their interactions with bio-systems and drug molecules are still unknown. The research work reported in this PhD thesis is aimed to understand the behavior of these polymers in solution and their interactions with biological interfaces and drug molecules using molecular dynamics simulations. Recently proposed models for the ether based polymers and their monomers were successfully tested in a wide range of non-aqueous solvents to establish their versatility. The thermodynamics and kinetics of the polymers and the monomers were first studied at simple water/n-heptane interface. Eventually the research was extended to study their properties at lipid bilayer interfaces. The percolation behavior of the ether based polymers and their monomers were studied using standard molecular dynamics, steered molecular dynamics and umbrella sampling simulations. It has been shown that the percolation of PPO chains through lipid bilayer is favored compared to their PEO counterparts. PEO chains do not have any preference for the interior of the bilayer and but the PPO chains prefer to stay inside the bilayer. PPO chains with length comparable to the width of the bilayer tend to span across the bilayer. Pluronics also show similar effect with PPO parts spanned along the width of the bilayer and the PEO blocks in the polar headgroup region and water in both sides of the bilayer. The potential of mean force barriers of bilayer percolation were found to be smaller for PPO chains of all lengths than their PEO counterparts. The last part of the project aimed to investigate the mechanism of interaction of Pluronics with hydrophobic drug molecules. Curcumin, a natural drug from the Indian spice turmeric, has recently attracted interest as potential multivalent drug for the treatment of different diseases comprising cancer and Alzheimer's disease. For its hydrophobic nature, it has low solubility in water and therefore efforts are directed to find suitable polymeric carrier. For all these reason, Curcumin was chosen as model of hydrophobic drug for my study. A suitable force field model for this drug was optimized and used to study its interaction with Pluronics. The results of these MD simulation studies evidenced the mechanism of drug-polymer aggregate formation in which Curcumin is embedded into a hydrophobic PPO core surrounded by a hydrophilic PEO shell. The findings of this thesis are useful in the better understanding of the interactions of block co-polymers with bio-membranes at atomic level. Moreover, they provide a better insight on the dynamics and thermodynamics of the drug encapsulation and delivery across cell membranes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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