Apparatus for Automated Continuous Hydrogen Deuterium Exchange Mass Spectrometry Measurements from Milliseconds to Hours.

Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a rapidly growing technique for protein characterization in industry and academia, complementing the "static" picture provided by classical structural biology with information about the dynamic structural changes that accompany biological function. Conventional hydrogen deuterium exchange experiments, carried out on commercially available systems, typically collect 4-5 exchange timepoints on a timescale ranging from tens of seconds to hours using a workflow that can require 24 h or more of continuous data collection for triplicate measurements. A small number of groups have developed setups for millisecond timescale HDX, allowing for the characterization of dynamic shifts in weakly structured or disordered regions of proteins.

Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies.

Neurodegeneration in Alzheimer's disease (AD) is defined by pathology featuring amyloid-β (Aβ) deposition in the brain. Aβ monomers themselves are generally considered to be nontoxic, but misfold into β-sheets and aggregate to form neurotoxic oligomers. One suggested strategy to treat AD is to prevent the formation of toxic oligomers.

A Unique Conformational Distortion Mechanism Drives Lipocalin 2 Binding to Bacterial Siderophores.

Lcn2 is a host defense protein induced via the innate immune response to sequester iron-loaded bacterial siderophores. However, excess or prolonged elevation of Lcn2 levels can induce adverse cellular effects, including oxidative stress and inflammation. In this work, we use Hydrogen-Deuterium eXchange (HDX) and Isothermal Titration Calorimetry (ITC) to characterize the binding interaction between Lcn2 and siderophores enterobactin and 2,3-DHBA, in the presence and absence of iron.

Exploring Amyloid-β Dimer Structure Using Molecular Dynamics Simulations.

A major hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides in the brains of people afflicted by the disease. The exact pathway to this catastrophic event is unknown. In this work, a total of 9.

d-Amino Acid Pseudopeptides as Potential Amyloid-Beta Aggregation Inhibitors.

A causative factor for neurotoxicity associated with Alzheimer's disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out to study the interaction of the pseudo-peptides with both Aβ (the core recognition site of Aβ) and full-length Aβ.