Continuous interdomain orientation distributions reveal components of binding thermodynamics,

by Yang Qi, Jeff Martin, Adam Barb, Francois Thelot, Anthony Yan, B. R. Donald*, and Terry Oas*

*Corresponding authors

bioRxiv 200238; (2017)
doi: https://doi.org/10.1101/200238

[Abstract, PDF, Supplementary Material]

and

Redefining Structure: New Approaches for
(1) Deep Topological Sampling of Protein Structures, and
(2) Continuous Probability Density Function for Biomolecular Interdomain Orientations,
by Yang Qi, Jeff Martin, Adam Barb, Francois Thelot, Anthony Yan, Terry Oas*, and B. R. Donald*.
Experimental NMR Conference (ENC). Pittsburgh, PA. April 12, 2016.
[ PDF]

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 (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation. Using the DoS representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions. 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 S. aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing components of binding thermodynamics. Such insights allow the dissection the dynamic structural components of functionally important intermolecular interactions. 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 (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation. Using the DoS representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions. 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 S. aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing components of binding thermodynamics. Such insights allow the dissection the dynamic structural components of functionally important intermolecular interactions.