Kinetics is a key aspect of the renowned protein folding problem. Here, we propose a comprehensive approach to folding kinetics where a polypeptide chain is assumed to behave as an elastic material described by the Hooke׳s law. A novel parameter called elastic-folding constant results from our model and is suggested to distinguish between protein with two-state and multi-state folding pathways. A contact-free descriptor, named folding degree, is introduced as a suitable structural feature to study protein-folding kinetics. This approach generalizes the observed correlations between varieties of structural descriptors with the folding rate constant. Additionally several comparisons among structural classes and folding mechanisms were carried out showing the good performance of our model with proteins of different types. The present model constitutes a simple rationale for the structural and energetic factors involved in protein folding kinetics.
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PNAS Nexus
January 2025
School of Chemistry & Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive NW, Atlanta, GA 30332, USA.
Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several antibodies that inhibit aggregation are approved or in clinical trials to treat Alzheimer's disease. Here, we developed antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma and cause early onset vision loss for several million individuals worldwide. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER).
View Article and Find Full Text PDFProtein Sci
January 2025
Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
Antibodies and antibody mimics are extensively used in the pharmaceutical industry, where stringent safety standards are required. Implementing heat sterilization during or after the manufacturing process could help prevent contamination by viruses and bacteria. However, conventional antibodies and antibody mimics are not suitable for heat sterilization because they irreversibly denature at high temperatures.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
Department of Biomedical Engineering, the Engineering Faculty, Tel Aviv University, Tel-Aviv, Israel.
The P-glycoprotein efflux pump, encoded by the MDR1 gene, is an ATP-driven transporter capable of expelling a diverse array of compounds from cells. Overexpression of this protein is implicated in the multi-drug resistant phenotype observed in various cancers. Numerous studies have attempted to decipher the impact of genetic variants within MDR1 on P-glycoprotein expression, functional activity, and clinical outcomes in cancer patients.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Institute for Physical Science and Technology, Biophysics Program, University of Maryland, College Park, Maryland 20742, USA.
Clustering is a type of machine learning technique, which is used to group huge amounts of data based on their similarity into separate groups or clusters. Clustering is a very important task that is nowadays used to analyze the huge and diverse amount of data coming out of molecular dynamics (MD) simulations. Typically, the data from the MD simulations in terms of their various frames in the trajectory are clustered into different groups and a representative element from each group is studied separately.
View Article and Find Full Text PDFWater Res
December 2024
Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Xiao Ling Wei 200, Nanjing 210094, Jiangsu, China. Electronic address:
High temperature (HT) shock is one of environmental stressors suppressing microalgal activities in microalgal wastewater bioremediation system. However, its inhibition mechanism and how to alleviate such suppression remain inadequately understood. This study confirmed a transient ferroptosis as a novel form of programmed cell death in a wastewater-indigenous Chlorella sp.
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