We propose a new type of transition network for modeling of protein dynamics. The nodes of the network correspond to the conformations taken from random sampling of equilibrium ensemble available, e.g., by Monte Carlo simulations. Although this approach does not provide absolute values of folding/unfolding rates, it allows identification of reaction pathways, transition state ensemble, and, eventually, intermediates. The new method is verified by a comparison with direct molecular dynamic simulations performed for a coarse-grained Gō-like model of proteins. As an illustrative example, we analyze kinetics of formation of a small β-hairpin (Trp zipper 1) in the all-atom representation.
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http://dx.doi.org/10.1063/1.3670106 | DOI Listing |
J Surg Educ
January 2025
Washington University of St. Louis, Department of Orthopaedic Surgery, St. Louis, Missouri.
Objective: Orthopedic residents are tasked with rapidly acquiring clinical and surgical skills, especially during their PGY-1 year. However, resource constraints and other factors frequently cause skills training to fall short of established guidelines. We aimed to design and evaluate a cross-institutional, month-long curriculum aimed at pooling resources to optimize training.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214.
Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Center for Environmental Economics - Montpellier (Univ Montpellier, CNRS, INRAE, Institut Agro), Montpellier 34000, France.
Collaborative management partnerships (CMPs) between state wildlife authorities and nonprofit conservation organizations to manage protected areas (PAs) have been used increasingly across Sub-Saharan Africa since the 2000s. They aim to attract funding, build capacity, and increase the environmental effectiveness of PAs. Our study documents the rise of CMPs, examines their current extent, and measures their effectiveness in protecting habitats.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210.
The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
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