ABSTRACT
Correct structural assignment of small molecules and natural products is critical for drug discovery and organic chemistry. Anisotropy-based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents. Here, we establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule-specific anisotropic NMR parameters. The quantitative correlation uses an accurate three-dimensional molecular alignment model that predicts residual dipolar couplings of small molecules aligned by poly(γ-benzyl-l-glutamate). The technique facilitates reliable determination of the correct stereoisomer and enables unequivocal, rapid determination of complex molecular structures from extremely sparse NMR data.
ABSTRACT
MOTIVATION: A large fraction of eukaryotic proteins contain unstructured tails or linkers. The presence of flexible regions allows these systems to experience a high level of mobility facilitating their biological function. The complex nature of protein rotation in such flexible modular systems precludes a straightforward application of hydrodynamic methods to calculate their rotational motional properties. We describe the workflow of HYdrodynamic CoUpling of Domains (HYCUD), a program for prediction of effective rotational correlation times in multidomain proteins. The usage of HYCUD is demonstrated by its application to the ribosomal protein L7/L12. Rotational correlation times predicted by HYCUD might be used to detect molecular switch events mediated by disorder-order transitions in interdomain linkers. AVAILABILITY AND IMPLEMENTATION: The source code and documentation are available at www.mpibpc.mpg.de/106144/software. CONTACT: mzwecks@gwdg.de or nare@nmr.mpibpc.mpg.de SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.
Subject(s)
Computational Biology/methods , Ribosomal Proteins/chemistry , Rotation , Software , Protein Structure, TertiaryABSTRACT
Time is of the essence: The rotational motion of biomolecules depends on intra- and intermolecular interactions and thus on distinct functional states. A new method, called HYCUD accurately predicts rotational correlation times in complex dynamic systems. It gives insights into the motional behavior of multidomain proteins in their free form and in supramolecular complexes.
