Dimerization of Full-Length Aβ-42 Peptide: A Comparison of Different Force Fields and Water Models.

Among the two isoforms of amyloid-β i. e., Aβ-40 and Aβ-42, Aβ-42 is more toxic due to its increased aggregation propensity.

Muco-Adhesive and Muco-Penetrative Formulations for the Oral Delivery of Insulin.

Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity, often associated with pancreatic β cells impairment, leads to hyperglycemia, a hallmark of diabetes. Type 1 diabetes (T1D) results from autoimmune destruction of β cells, while type 2 diabetes (T2D) stems from genetic, environmental, and lifestyle factors causing β cell dysfunction and insulin resistance.

Molecular Dynamics Simulation Study of the Self-Assembly of Tau-Derived PHF6 and Its Inhibition by Oleuropein Aglycone from Extra Virgin Olive Oil.

Alzheimer's disease (AD) and other taupathies are neurodegenerative disorders associated with the amyloid deposition of the Tau protein in the brain. This amyloid formation may be inhibited by small molecules, which is recognized as one of the best therapeutic strategies to stop the progression of the disease. This work focuses on the small nucleating segment, hexapeptide-paired helical filament 6 (PHF6), responsible for Tau aggregation.

Impact of Oxysterols in Age-Related Disorders and Strategies to Alleviate Adverse Effects.

Oxysterols or cholesterol oxidation products are a class of molecules with the sterol moiety, derived from oxidative reaction of cholesterol through enzymatic and non-enzymatic processes. They are widely reported in animal-origin foods and prove significant involvement in the regulation of cholesterol homeostasis, lipid transport, cellular signaling, and other physiological processes. Reports of oxysterol-mediated cytotoxicity are in abundance and thus consequently implicated in several age-related and lifestyle disorders such as cardiovascular diseases, bone disorders, pancreatic disorders, age-related macular degeneration, cataract, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, and some types of cancers.

Curvature induced structural changes of the chicken villin headpiece subdomain by single walled carbon nanotubes.

Carbon nanotubes (CNTs) are identified as potential candidates for drug and biomolecular loading and delivery. CNTs of different chiralities have different diameters, which may significantly affect their abilities to interact with different types of biomolecules. Herein, we employ classical molecular dynamics simulation to provide insight into the curvature-dependent interactions between a model protein, chicken villin headpiece subdomain (HP36), with CNTs having chiralities (8,8), (12,12), and (20,20).

Molecular insights into the urea-choline--sulfate interactions in aqueous solution.

Urea and choline--sulfate (COS) are both osmolytes, but have opposite effects on protein structure. Urea has been well-known for years to destabilize protein structure. Though COS has been revealed as an osmoprotective molecule against urea induced denaturation of proteins, the mechanism of this compensation is still unexplored.

Controlling the self-assembly of human calcitonin: a theoretical approach using molecular dynamics simulations.

Human calcitonin (hCT) is a 32-residue amino acid poly-peptide hormone which is secreted by the C-cells (also known as parafollicular cells) of thyroid glands. It acts to inhibit osteoclast cell hormones by reducing the cell function and regulating calcium and phosphate in blood. hCT has a high tendency to assemble into protofilaments with β-sheet conformations.

Molecular Insight into the Effects of Enhanced Hydrophobicity on Amyloid-like Aggregation.

Generally, hydrophobic amino acids provide hydrophobic interactions during peptide aggregation. However, besides the hydrophobic amino acids, some hydrophilic amino acids, such as glutamine, are also considered to be essential elements in many self-aggregating peptides. For example, huntingtin contains polyglutamine at its N-terminus and the yeast prion Sup35 protein has the GNNQQNY sequence, a peptide well-known for its ability for amyloid fibril formation.

In silico study of osmolytic effects of choline-O-sulfate on urea induced unfolding of Trp-cage mini-protein: An atomistic view from replica exchange molecular dynamics simulation.

The event of protein folding is associated with essential biological functionalities and unfolding of protein native state can cause intra-cellular toxicity leading to biological dysfunctions and even cell death. The present study discusses the folding-unfolding equilibrium of the small globular protein Trp-cage in presence of denaturing and protecting osmolytes urea and choline-O-sulfate (COS), respectively, employing Replica Exchange Molecular Dynamics (REMD), extensive free energy calculations and temperature scanned free energy landscapes. It is shown that, while 6 M urea quite easily denatures the protein, 0.

The conformational stability of terminal helices of λ-repressor protein in aqueous dodine and choline-O-sulfate solutions.

In this article, we have ventured into the denaturation of fast folding λ-repressor protein at a millimolar concentration of dodine and henceforth, evaluated the candidature of choline-O-sulfate as a protecting osmolyte against it, employing classical molecular dynamics simulations. Our simulation results show that, the terminal helices of λ-repressor protein get unfolded in presence of ∼15 mM dodine while 0.5 M and higher concentration of COS can prevent this deleterious effect of dodine.

Molecular dynamics simulation study on the inhibitory effects of choline-O-sulfate on hIAPP protofibrilation.

Type 2 diabetes mellitus (T2Dm) is a neurodegenerative disease, which occurs due to the self-association of human islet amyloid polypeptide (hIAPP), also known as human amylin. It was reported experimentally that choline-O-sulfate (COS), a small organic molecule having a tertiary amino group and sulfate group, can prevent the aggregation of human amylin without providing the mechanism of the action of COS in the inhibition process. In this work, we investigate the influence of COS on the full-length hIAPP peptide by performing 500 ns classical molecular dynamics simulations.

Inhibitory Effect of Choline- O-sulfate on Aβ Peptide Aggregation: A Molecular Dynamics Simulation Study.

The aggregation of Aβ peptide, the smallest fragment of full-length Aβ with seven residues, plays a very crucial role in Aβ toxicity, hence causing Alzheimer's disease. Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with brain disorder, and currently there is no treatment available in the market to cure it permanently. So, drug design for the curable treatment of AD is a very challenging problem.

How Does Aqueous Choline- O-Sulfate Solution Nullify the Action of Urea in Protein Denaturation?

Choline- O-sulfate (COS) acts as a protecting osmolyte in several plants, fungal, and bacterial species. Classical molecular dynamics simulation is performed to examine the molecular mechanism by which COS molecules counteract urea-conferred denaturation of the S-peptide analogue. The calculations of root mean square deviation, the radius of gyration of the C atom, and the solvent accessible surface area of the peptide heavy atoms imply that the 4-12 residues of the peptide in pure water remain in helical conformation at 310 K temperature.