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Photo Marie Skepö

Marie Skepö

Professor

Photo Marie Skepö

Evaluating Models of Varying Complexity of Crowded Intrinsically Disordered Protein Solutions against SAXS

Author

  • Eric Fagerberg
  • Samuel Lenton
  • Marie Skepö

Summary, in English

Intrinsically disordered proteins (IDPs) adopt heterogeneous conformational ensembles in solution. The properties of the conformational ensemble are dependent upon the solution conditions, including the presence of ions, temperature, and crowding, and often directly impact biological function. Many in vitro investigations focus on the properties of IDPs under dilute conditions, rather than the crowded environment found in vivo. Due to their heterogeneous nature, the study of IDPs under crowded conditions is challenging both experimentally and computationally. Despite this, such studies are worth pursuing due to the insight gained into biologically relevant phenomena. Here, we study the highly charged IDP Histatin 5 under self-crowded conditions in low and high salt conditions. A combination of small-angle X-ray scattering and different simulation models, spanning a range of computational complexity and detail, is used. Most models are found to have limited application when compared to results from experiments. The best performing model is the highly coarse-grained, bead-necklace model. This model shows that Histatin 5 has a conserved radius of gyration and a decreasing flexibility with increasing protein concentration. Due to its computational efficiency, we propose that it is a suitable model to study crowded IDP solutions, despite its simplicity.

Department/s

  • Computational Chemistry
  • LINXS - Institute of advanced Neutron and X-ray Science
  • eSSENCE: The e-Science Collaboration

Publishing year

2019

Language

English

Pages

6968-6983

Publication/Series

Journal of Chemical Theory and Computation

Volume

15

Issue

12

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Theoretical Chemistry (including Computational Chemistry)

Status

Published

ISBN/ISSN/Other

  • ISSN: 1549-9618