Continuous Interdomain Orientation Distributions Reveal Components of Binding Thermodynamics.

Journal Article (Journal Article)

The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings, represented as a continuous conformational distribution, and visualized using the disk-on-sphere representation. Using the disk-on-sphere representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions.This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity of Staphylococcus aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing the reorientational components of binding thermodynamics. Such insights allow for the dissection of the dynamic structural components of functionally important intermolecular interactions.

Full Text

Duke Authors

Cited Authors

  • Qi, Y; Martin, JW; Barb, AW; Thélot, F; Yan, AK; Donald, BR; Oas, TG

Published Date

  • September 14, 2018

Published In

Volume / Issue

  • 430 / 18 Pt B

Start / End Page

  • 3412 - 3426

PubMed ID

  • 29924964

Pubmed Central ID

  • PMC6115201

Electronic International Standard Serial Number (EISSN)

  • 1089-8638

Digital Object Identifier (DOI)

  • 10.1016/j.jmb.2018.06.022


  • eng

Conference Location

  • England