Dynamic single-molecule force spectroscopy (SMFS) is a powerful method to characterize the mechanical stability of biomolecules. We address the problem that the standard manner of reporting the extracted energy landscape parameters does not reveal the intrinsic statistical errors associated with them. This problem becomes particularly relevant when SMFS is used to compare two or more different molecular systems. Here, we propose two methods that allow for a straightforward test of statistical significance. We illustrate the power of the methods by applying them to the experimental results obtained for three dimeric coiled coils of different lengths. Both methods are general and may be applied to any problem involving the fit of models with two correlated parameters.
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http://dx.doi.org/10.1063/1.5055071 | DOI Listing |
Elife
January 2025
Eikon Therapeutics Inc, Hayward, United States.
The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis.
View Article and Find Full Text PDFNat Genet
January 2025
Institute for Integrative Systems Biology, Spanish National Research Council, Paterna, Spain.
The advent of single-molecule, long-read sequencing (LRS) technologies by Oxford Nanopore Technologies and Pacific Biosciences has revolutionized genomics, transcriptomics and, more recently, epigenomics research. These technologies offer distinct advantages, including the direct detection of methylated DNA and simultaneous assessment of DNA sequences spanning multiple kilobases along with their modifications at the single-molecule level. This has enabled the development of new assays for analyzing chromatin states and made it possible to integrate data for DNA methylation, chromatin accessibility, transcription factor binding and histone modifications, thereby facilitating comprehensive epigenomic profiling.
View Article and Find Full Text PDFProtein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.
View Article and Find Full Text PDFAcc Chem Res
January 2025
Laboratory for Chemistry and Life Science (CLS), Institute of Integrated Research, Institute of Science Tokyo, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
ConspectusThe design of properties and functions of molecular assemblies requires not only a proper choice of building blocks but also control over their packing arrangements. A highly versatile unit in this context is a particular type of triptycene with substituents at the 1,8,13-positions, called tripodal triptycene, which offers predictable molecular packing and multiple functionalization sites, both at the opposite 4,5,16- or 10 (bridgehead)-positions. These triptycene building blocks are capable of two-dimensional (2D) nested hexagonal packing, leading to the formation of 2D sheets, which undergo one-dimensional (1D) stacking into well-defined "2D+1D" structures.
View Article and Find Full Text PDFCurr Opin Cell Biol
January 2025
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, GA 30322, USA. Electronic address:
Twinfilin is an evolutionarily conserved actin-binding protein initially mischaracterized as a tyrosine kinase but later recognized as a key regulator of cellular actin dynamics. As a member of the ADF-H family, twinfilin binds both actin monomers and filaments. Its role in sequestering G-actin is well-established, but its effects on actin filaments have been debated.
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