DNA hairpin molecules with periodic base sequences can be expected to exhibit a regular coarse-grained free energy landscape (FEL) as a function of the number of open base pairs and applied mechanical force. Using a commonly employed model, we first analyze for which types of sequences a particularly simple landscape structure is predicted, where forward and backward energy barriers between partly unfolded states are decreasing linearly with force. Stochastic unfolding trajectories for such molecules with simple FEL are subsequently generated by kinetic Monte Carlo simulations. Introducing probabilities that can be sampled from these trajectories, it is shown how the parameters characterizing the FEL can be estimated. Already 300 trajectories, as typically generated in experiments, provide faithful results for the FEL parameters.
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http://dx.doi.org/10.1088/0953-8984/26/20/205102 | DOI Listing |
Biophys J
January 2025
Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:
The Hsp100 family of protein disaggregases play important roles in maintaining protein homeostasis in cells. E. coli ClpB is an Hsp100 protein that solubilizes protein aggregates.
View Article and Find Full Text PDFBiomolecules
January 2025
Institute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Street, Novosibirsk 630090, Russia.
In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, N/N, O/O, and C/C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds N-H⋯O=C due to heavy isotope substitution decreases in the row H/D >> N/N > O/O > C/C.
View Article and Find Full Text PDFAntioxidants (Basel)
January 2025
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy.
Investigating amyloid-β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1-42) peptide to misfold in solution, correlated to the aetiology of Alzheimer's disease (AD), is one of the main hindrances to characterising its aggregation kinetics in a cell-mimetic environment. Moreover, the Aβ(1-42) aggregation triggers the unfolded protein response (UPR) in the endoplasmic reticulum (ER), leading to cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage cellular components and trigger inflammation.
View Article and Find Full Text PDFKidney Int
February 2025
Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel Switzerland. Electronic address:
BK polyomavirus remains a vexing issue in kidney transplantation. There are no antiviral drugs, and solely reducing immunosuppression is recommended for management. However, evidence from randomized controlled studies lacks defining clearance of BK polyomavirus-DNAemia and/or nephropathy as a primary outcome.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Department of Biosciences, University of Milan, Italy; Institute of Molecular and Translational Cardiology, IRCCS, Policlinico San Donato, Milan, Italy. Electronic address:
Light chain (AL) amyloidosis is the most common systemic amyloid disease characterized by abnormal accumulation of amyloid fibrils derived from immunoglobulin light chains (LCs). Both full-length (FL) LCs and their isolated variable (VL) and constant (CL) domains contribute to amyloid deposits in multiple organs, with the VL domain predominantly forming the fibril core. However, the role and interplay of these domains in amyloid aggregation and toxicity are poorly understood.
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