Deeper Insight of the Conformational Ensemble of Intrinsically Disordered Proteins.

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.