The recently discovered supersymmetric generalizations of the Langevin dynamics and Kramers equation can be utilized for the exploration of free-energy landscapes of systems whose large time-scale separation hampers the usefulness of standard molecular dynamics techniques. The first realistic application is here presented. The system chosen is a minimalist model for a short alanine peptide exhibiting a helix-coil transition.
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http://dx.doi.org/10.1103/PhysRevE.75.046707 | DOI Listing |
Sci Rep
January 2025
Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, El‑Sadat, Egypt.
PLoS One
January 2025
Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
The ongoing increase in the prevalence and mutation rate of the influenza virus remains a critical global health issue. A promising strategy for antiviral drug development involves targeting the RNA-dependent RNA polymerase, specifically the PB2-cap binding domain of Influenza A H5N1. This study employs an in-silico approach to inhibit this domain, crucial for viral replication, using potential inhibitors derived from marine bacterial compounds.
View Article and Find Full Text PDFProtein Sci
February 2025
Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
Loz1 is a zinc-responsive transcription factor in fission yeast that maintains cellular zinc homeostasis by repressing the expression of genes required for zinc uptake in high zinc conditions. Previous deletion analysis of Loz1 found a region containing two tandem CH zinc-fingers and an upstream "accessory domain" rich in histidine, lysine, and arginine residues to be sufficient for zinc-dependent DNA binding and gene repression. Here we report unexpected biophysical properties of this pair of seemingly classical CH zinc fingers.
View Article and Find Full Text PDFBiophys Chem
January 2025
Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Kolkata 700106, India. Electronic address:
Quantitative characterization of protein conformational landscapes is a computationally challenging task due to their high dimensionality and inherent complexity. In this study, we systematically benchmark several widely used dimensionality reduction and clustering methods to analyze the conformational states of the Trp-Cage mini-protein, a model system with well-documented folding dynamics. Dimensionality reduction techniques, including Principal Component Analysis (PCA), Time-lagged Independent Component Analysis (TICA), and Variational Autoencoders (VAE), were employed to project the high-dimensional free energy landscape onto 2D spaces for visualization.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry, New York University, New York, NY 10003.
Frameshifting is an essential mechanism employed by many viruses including coronaviruses to produce viral proteins from a compact RNA genome. It is facilitated by specific RNA folds in the frameshift element (FSE), which has emerged as an important therapeutic target. For SARS-CoV-2, a specific 3-stem pseudoknot has been identified to stimulate frameshifting.
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