Deeper Insight of the Conformational Ensemble of Intrinsically Disordered Proteins

Summary, in English

It is generally known that, unlike structured proteins, intrinsically disordered proteins, IDPs, exhibit various structures and conformers, the so-called conformational ensemble, CoE. This study aims to better understand the conformers that make up the IDP ensemble by decomposing the CoE into groups separated by their radius of gyration, R_g. A common approach to studying CoE for IDPs is to use low-resolution techniques, such as small-angle scattering, and combine those with computer simulations on different length scales. Herein, the well-studied antimicrobial saliva protein histatin 5 was utilized as a model peptide for an IDP; the average intensity curves were obtained from small-angle X-ray scattering; and compared with fully atomistic, explicit water, molecular dynamics simulations; then, the intensity curve was decomposed with respect to the different R_g values; and their secondary structure propensities were investigated. We foresee that this approach can provide important information on the CoE and the individual conformers within; in that case, it will serve as an additional tool for understanding the IDP structure-function relationship on a more detailed level.

• Author: Oskar Svensson; Michael J. Bakker; Marie Skepö
• Department/s: Computational Chemistry; eSSENCE: The e-Science Collaboration; NanoLund: Centre for Nanoscience; LTH Profile Area: Nanoscience and Semiconductor Technology; Department of Chemistry
• Publishing year: 2024-08
• Language: English
• Pages: 6105-6114
• Publication/Series: Journal of Chemical Information and Modeling
• Volume: 64
• Issue: 15
• Links: http://dx.doi.org/10.1021/acs.jcim.4c00941
• Document type: Journal article
• Publisher: The American Chemical Society (ACS)
• Topic: Theoretical Chemistry (including Computational Chemistry); Physical Chemistry (including Surface- and Colloid Chemistry)
• Status: Published
• ISBN/ISSN/Other: ISSN: 1549-9596