Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Submitted Manuscript

Publication Date

9-14-2018

Journal or Book Title

Journal of Molecular Biology

Volume

430

Issue

18, Part B

First Page

3412

Last Page

3426

DOI

10.1016/j.jmb.2018.06.022

Abstract

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 factorcontributing 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.

Comments

This is a manuscript of an article published as Qi, Yang, Jeffrey W. Martin, Adam W. Barb, Francois Thelot, Anthony K. Yan, Bruce R. Donald, and Terrence G. Oas. "Continuous interdomain orientation distributions reveal components of binding thermodynamics." Journal of molecular biology 430, no. 18 (2018): 3412-3426. doi: 10.1016/j.jmb.2018.06.022. Posted with permission.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

Published Version

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