1,721,002 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
Cosolvent, ions, and temperature effects on the structural properties of cecropin A-Magainin 2 hybrid peptide in solutions
No full textAntimicrobial peptides are promising alternative to traditional antibiotics and antitumor drugs for the battle against new antibiotic resistant bacteria strains and cancer maladies. The study of their structural and dynamics properties at physiological conditions can help to understand their stability, delivery mechanisms, and activity in the human body. In this article, we have used molecular dynamics simulations to study the effects of solvent environment, temperature, ions concentration, and peptide concentration on the structural properties of the antimicrobial hybrid peptide Cecropin A-Magainin 2. In TFE/water mixtures, the structure of the peptide retained α-helix contents and an average hinge angle in close agreement with the experimental NMR and CD measurements reported in literature. Compared to the TFE/water mixture, the peptide simulated at the same ionic concentration lost most of its α-helix structure. The increase of peptide concentration at both 300 and 310 K resulted in the peptide aggregation. The peptides in the complex retained the initial N-ter α-helix segment during all the simulation. The α-helix stabilization is further enhanced in the high salt concentration simulations. The peptide aggregation was not observed in TFE/water mixture simulations and, the peptide aggregate, obtained from the water simulation, simulated in the same conditions did dissolve within few tens of nanoseconds. The results of this study provide insights at molecular level on the structural and dynamics properties of the CA-MA peptide at physiological and membrane mimic conditions that can help to better understand its delivery and interaction with biological interfaces
Coating mechanisms of single-walled carbon nanotube by linear polyether surfactants: Insights from computer simulations
No full textThe noncovalent coating of carbon-based nanomaterials, such as carbon nanotubes, has important applications in nanotechnology and nanomedicine. The molecular modeling of this process can clarify its mechanism and provide a tool for the design of novel materials. In this paper, the coating mechanism of single-walled carbon nanotubes (SWCNT) in aqueous solutions by 1,2-dimethoxyethane oxide (DME), 1,2-dimethoxypropane oxide (DMP), poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) pentamers, and L64 triblock copolymer chains have been studied using molecular dynamics (MD) simulations. The results suggest a preferential binding to the SWCNT surface of the DMP molecules with respect to DME mainly driven by their difference in hydrophobicity. For the longer pentamers, it depends by the chain conformation. PPO isomers with radius of gyration larger than PEO pentamers bind more tightly than those with more compact conformation. In the case of the L64 triblock copolymer, the coating of the SWCNT surface produces a shell of PPO blocks with the PEO chains protruding into bulk water as expected from the so-called nonwrapping binding mechanism of SWCNT. In addition, the polymer coating, in qualitative agreement with experimental evidence on the poor capability of the L64 to disperse SWCNT, do not prevent the formation of CNT aggregates. © 2014 American Chemical Society
Interplay between hydrophobic cluster and loop propensity in beta-hairpin formation: A mechanistic study
No full textWe investigated the structural determinants of the stability of a
designed P-hairpin containing a natural hydrophobic cluster from the
protein GB1 and a D-Pro-Gly turn forming sequence. The results of our
simulations shed light on the factors leading to an ordered secondary
structure in a model peptide: in particular, the importance of the
so-called diagonal interactions in forming a stable hydrophobic nucleus
in the beta-hairpin, together with the more obvious lateral
interactions, is examined. With the use of long timescale MD simulations
in explicit water, we show the role of diagonal interactions in driving
the peptide to the correct folded structure (formation of the
hydrophobic core with Trp 2, Tyr 4, and Phe 9 in the first stages of
refolding) and in keeping it in the ensemble of folded conformations.
The combination of the stabilizing effects of the D-Pro-Gly turn
sequence and of the hydrophobic nucleus formation thus favors the
attainment of an ordered secondary structure compatible with the one
determined experimentally. Moreover, our data underline the importance
of the juxtapositions of the side chains of amino acids not directly
facing each other in the three-dimensional structure. The combination of
these interactions forces the peptide to sample a nonrandom portion of
the conformational space, as can be seen in the rapid collapse to an
ordered structure in the refolding simulation, and shows that the
unfolded state can be closely correlated to the folded ensemble of
structures, at least in the case of small model peptides
Investigating the accessibility of the closed domain conformation of citrate synthase using essential dynamics sampling
No full textSynthetic Polymers and Biomembranes. How Do They Interact?: Atomistic Molecular Dynamics Simulation Study of PEO in Contact with a DMPC Lipid Bilayer
No full textA theoretical model for the folding/unfolding thermodynamics of single-domain proteins, based on the quasi-Gaussian entropy theory
No full textThe quasi-Gaussian entropy (QGE) theory was used to formulate a statistical mechanical model describing the thermodynamics of the folding/unfolding process of single-domain proteins. The model was parametrized using experimental data obtained from differential scanning calorimetry (DSC) of a set of proteins. The results showed that the model is able to reproduce the experimental behavior in the usual temperature range, for all the analyzed proteins. Furthermore, a remarkable similarity of some parameters of the model, when normalized per residue and corresponding to well-defined physical properties, was found. Interestingly, at low temperature, the model provides cold denaturation features for all the proteins. Finally, a general description of the folding/unfolding process and stability, based on the physical view provided by the model, is discussed
Folding and stability of the three-stranded beta-sheet peptide betanova: Insights from molecular dynamics simulations
No full textThe dynamics of the three-stranded beta-sheet peptide Betanova has been studied at four different temperatures (280, 300, 350, and 450 K by molecular dynamics simulation techniques, in explicit water. Two 20-ns simulations at 280 K indicate that the peptide remains very flexible under "folding" conditions sampling a range of conformations that together satisfy the nuclear magnetic resonance (NMR)-derived experimental constraints. Two simulations at 300 K (above the experimental folding, temperature) of 20 ns each show partial formation of "native"-like structure, which also satisfies most of the NOE constraints at 280 K. At higher temperature, the presence of compact states, in which a series of hydrophobic contacts remain present, are observed. This is consistent with experimental observations regarding the role of hydrophobic contacts in determining the peptide's stability and in initiating the formation of turns and loops. A set of different structures is shown to satisfy NMR-derived distance restraints and a possible mechanism for the folding of the peptide into the NMR-determined structure is proposed. (C) 2002 Wiley-Liss Inc
Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: A molecular dynamics study
No full textMolecular dynamics simulation techniques have been used to investigate
the effect of 2,2,2-trifluoroethanol (TFE) as a cosolvent on the
stability of three different secondary structure-forming peptides: the
a-helix from Melittin, the three-stranded 13-sheet peptide Betanova, and
the beta-hairpin 41-56 from the B1 domain of protein G. The peptides
were studied in pure water and 30\% (vol/vol) TFE/water mixtures at 300
K. The simulations suggest that the stabilizing effect of TFE is induced
by the preferential aggregation of TFE molecules around the peptides.
This coating displaces water, thereby removing alternative
hydrogen-bonding partners and providing a low dielectric environment
that favors the formation of intrapeptide hydrogen bonds. Because TFE
interacts only weakly with nonpolar residues, hydrophobic interactions
within the peptides are not disrupted. As a consequence, TFE promotes
stability rather than inducing denaturation
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