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Detailed descriptions of atomic coordinates and motions are required for an understanding of protein dynamics and their relation to molecular recognition, catalytic function, and allostery. Historically, NMR relaxation measurements have played a dominant role in the determination of the amplitudes and timescales (picosecond-nanosecond) of bond vector(More)
In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic(More)
Correlated motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. The mechanisms that underlie these processes remain largely unknown due mainly to limitations in their direct detection. Here, based on a detailed analysis of protein structures deposited in the protein data bank, as well as on(More)
We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of(More)
The synchronization of native state motions as they transition between microstates influences catalysis kinetics, mediates allosteric interactions, and reduces the conformational entropy of proteins. However, it has proven difficult to describe native microstates because they are usually minimally frustrated and may interconvert on the micro- to millisecond(More)
Long-range correlated motions in proteins are candidate mechanisms for processes that require information transfer across protein structures, such as allostery and signal transduction. However, the observation of backbone correlations between distant residues has remained elusive, and only local correlations have been revealed using residual dipolar(More)
Molecular recognition plays a central role in many biological processes. For enzymatic reactions and slow protein–protein recognition events, turnover rates and on-rates in the millisecond to second time scale have been connected to internal protein dynamics detected with atomic resolution by NMR spectroscopy, and in particular conformational sampling could(More)
Residual dipolar couplings (RDCs) are unique probes of the structural and dynamical properties of biomolecules on the sub-millisecond time scale that can be used as restraints in ensemble molecular dynamics simulations to study the relationship between macromolecular motion and biological function. To date, however, this powerful strategy is applicable only(More)
Non-uniform sampling (NUS) in NMR spectroscopy is a recognized and powerful tool to minimize acquisition time. Recent advances in reconstruction methodologies are paving the way for the use of NUS in quantitative applications, where accurate measurement of peak intensities is crucial. The presence or absence of NUS artifacts in reconstructed spectra(More)
Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by(More)