Small-angle X-ray scattering (SAXS) experiments are widely used for the characterization of biological macromolecules in solution. SAXS patterns contain information on the size and shape of dissolved particles in nanometer resolution. Here we propose a method for primary SAXS data analysis based on the application of artificial neural networks (NNs). Trained on synthetic SAXS data, the feedforward NNs are able to reliably predict molecular weight and maximum intraparticle distance (D) directly from the experimental data. The method is applicable to data from monodisperse solutions of folded proteins, intrinsically disordered proteins, and nucleic acids. Extensive tests on synthetic SAXS data generated in various angular ranges with varying levels of noise demonstrated a higher accuracy and better robustness of the NN approach compared to the existing methods.
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http://dx.doi.org/10.1016/j.str.2022.03.011 | DOI Listing |
While novel deep learning and statistics-based techniques predict accurate structural models for proteins and non-coding RNA, describing their macromolecular conformations in solution is still challenging. Small-angle X-ray scattering (SAXS) in solution is an efficient technique to validate structural predictions by comparing the experimental SAXS profile with those calculated from predicted structures. There are two main challenges in comparing SAXS profiles to RNA structures: the structures often lack cations necessary for stability and charge neutralization, and a single structure inadequately represents the conformational plasticity of RNA.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since the success of Patisiran, the first siRNA-LNP therapeutic, and the mRNA vaccines that emerged during the COVID-19 pandemic. Designing LNPs with specific targeting, high potency, and minimal side effects is crucial for their successful clinical use.
View Article and Find Full Text PDFJACS Au
December 2024
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
It has become increasingly evident that the conformational distributions of intrinsically disordered proteins or regions are strongly dependent on their amino acid compositions and sequence. To facilitate a systematic investigation of these sequence-ensemble relationships, we selected a set of 16 naturally occurring intrinsically disordered regions of identical length but with large differences in amino acid composition, hydrophobicity, and charge patterning. We probed their conformational ensembles with single-molecule Förster resonance energy transfer (FRET), complemented by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy as well as small-angle X-ray scattering (SAXS).
View Article and Find Full Text PDFBiophys J
December 2024
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address:
Advanced deep learning and statistical methods can predict structural models for RNA molecules. However, RNAs are flexible, and it remains difficult to describe their macromolecular conformations in solutions where varying conditions can induce conformational changes. Small-angle x-ray scattering (SAXS) in solution is an efficient technique to validate structural predictions by comparing the experimental SAXS profile with those calculated from predicted structures.
View Article and Find Full Text PDFBiophys J
December 2024
Institute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori, Sennan-gun, Osaka 590-0494 Japan. Electronic address:
Intrinsically disordered proteins (IDPs) show structural changes stimulated by changes in external conditions. This study aims to reveal the temperature dependence of the structure and dynamics of the intrinsically disordered region of Hef, one of the typical IDPs, using an integrative approach. Small-angle X-ray scattering (SAXS) and circular dichroism (CD) studies revealed that the radius of gyration and ellipticity at 222 nm remained constant up to 313-323 K, followed by a decline above this temperature range.
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