Continuous interdomain orientation distributions reveal components of binding thermodynamics

التفاصيل البيبلوغرافية
العنوان: Continuous interdomain orientation distributions reveal components of binding thermodynamics
المؤلفون: Adam W. Barb, Jeffrey W. Martin, Terrence G. Oas, François Thélot, Yang Qi, Bruce R. Donald, Anthony K. Yan
بيانات النشر: Cold Spring Harbor Laboratory, 2017.
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Models, Molecular, genetic structures, Protein Conformation, Staphylococcal protein, Thermodynamics, Probability density function, 010402 general chemistry, 01 natural sciences, Article, 03 medical and health sciences, Structural Biology, Protein Interaction Domains and Motifs, Representation (mathematics), Staphylococcal Protein A, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, Physics, 0303 health sciences, Intermolecular force, Representation (systemics), Proteins, Function (mathematics), Mixture model, Pathogenicity, 0104 chemical sciences, Orientation (vector space), 030104 developmental biology, Distribution function, Distribution (mathematics), Residual dipolar coupling
الوصف: 1AbstractThe 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. 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 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.
DOI: 10.1101/200238
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d68bb45670946bd205e3ca868c31f4d9
https://doi.org/10.1101/200238
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....d68bb45670946bd205e3ca868c31f4d9
قاعدة البيانات: OpenAIRE