Dataset Information

How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

ABSTRACT: Progressive cerebral deposition of amyloid beta occurs in Alzheimers disease and during the aging of certain mammals (human, monkey, dog, bear, cow, cat) but not others (rat, mouse). It is possibly due to different amino acid sequences at positions 5, 10 and 13. To address this issue, we performed series of 100 ns long trajectories (each trajectory was run twice with different initial velocity distribution) on amyloid beta (1-42) with the human and rat amino acid sequence in three different environments: water with only counter ions, water with NaCl at a concentration of 0.15 M as a model of intracellular Na(+) concentration at steady state, and water with NaCl at a concentration of 0.30 M as a model of intracellular Na(+) concentration under stimulated conditions. We analyzed secondary structure stability, internal hydrogen bonds, and residual fluctuation. It was observed that the change in ionic strength affects the stability of internal hydrogen bonds. Increasing the ionic strength increases atomic fluctuation in the hydrophobic core of the human amyloid, and decreases the atomic fluctuation in the case of rat amyloid. The secondary structure analyses show a stable ?-helix part between residues 10 and 20. However, C-terminus of investigated amyloids is much more flexible showing no stable secondary structure elements. Increasing ionic strength of the solvent leads to decreasing stability of the secondary structural elements. The difference in conformational behavior of the three amino acids at position 5, 10 and 13 for human and rat amyloids significantly changes the conformational behavior of the whole peptide.

SUBMITTER: Kriz Z

PROVIDER: S-EPMC3662769 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

Kříž Zdeněk Z Klusák Jiří J Krištofíková Zdena Z Koča Jaroslav J

PloS one 20130523 5

Progressive cerebral deposition of amyloid beta occurs in Alzheimers disease and during the aging of certain mammals (human, monkey, dog, bear, cow, cat) but not others (rat, mouse). It is possibly due to different amino acid sequences at positions 5, 10 and 13. To address this issue, we performed series of 100 ns long trajectories (each trajectory was run twice with different initial velocity distribution) on amyloid beta (1-42) with the human and rat amino acid sequence in three different envi ...[more]

PMID: 23717395

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Project description:The use of covalently crosslinked nanogels for applications in biology and medicine is dependent on their properties and characteristics, which often change because of the biological media involved. Understanding the role of salts, ionic strength and pH in altering specific properties is key to progress in this area. We studied the effect of both chemical structure and media environment on the thermoresponsive behavior of nanogels. A small library of methylenebisacrylamide (MBA) crosslinked nanogels were prepared using N-isopropylacrylamide (NIPAM) or N-n-propylacrylamide (NPAM), in combination with functional monomers N-hydroxyethylacrylamide (HEAM) and N-acryloyl-l-proline (APrOH). The thermoresponsive properties of nanogels were evaluated in phosphate buffer, tris-acetate buffer and Ringer HEPES, with varying concentrations and ionic strengths. The presence of ions facilitates the phase separation of nanogels, and this "salting-out" effect strongly depends on the electrolyte concentration as well as the specificity of individual anions, e.g., their positions in the Hofmeister series. A subtle change in the chemical structure of the side chain of the monomer from NIPAM to NPAM leads to a reduction of the volume phase transition temperature (VPTT) value by ~10 °C. The addition of hydrophilic comonomers such as HEAM, on the other hand, causes a ~20 °C shift in VPTT to higher values. The data highlight the significant role played by the chemical structure of the monomers used, with hydrophobicity and rigidity closely interlinked in determining thermoresponsive behavior. Furthermore, the volume phase transition temperature (VPTT) of nanogels copolymerized with ionizable APrOH comonomer can be tailored by changes in the pH of buffer solutions. This temperature-controlled phase transition is driven by intricate interplay involving the entropy of mixing, electrostatic interactions, conformational transitions, and structural rigidity. These results highlight the importance of understanding the physiochemical properties and behavior of covalently crosslinked nanogels in a biological environment prior to their applications in life-science, such as temperature/pH-triggered drug delivery systems.

Dataset Information

How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

Publications

How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

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