NMR View is a computer program designed for the visualization and analysis of NMR data. It allows the user to interact with a practically unlimited number of 2D, 3D and 4D NMR data files. Any number of spectral windows can be displayed on the screen in any size and location. Automatic peak picking and facilitated peak analysis features are included to aid in the assignment of complex NMR spectra. NMR View provides structure analysis features and data transfer to and from structure generation programs, allowing for a tight coupling between spectral analysis and structure generation. Visual correlation between structures and spectra can be done with the Molecular Data Viewer, a molecular graphics program with bidirectional communication to NMR View. The user interface can be customized and a command language is provided to allow for the automation of various tasks.

Nuclear magnetic resonance (NMR) experiments on macromolecules can generate a tremendous amount of data that must be analyzed and correlated to generate conclusions about the structure and dynamics of the molecular system. NMRView is a computer program that is designed to be useful in visualizing and analyzing these data. NMRView works with various types of NMR datasets and can have multiple datasets and display windows opened simultaneously. Virtually all actions of the program can be controlled through the Tcl scripting language, and new graphical user interface components can be added with the Tk toolkit. NMR spectral peaks can be analyzed and assigned. A suite of tools exists within NMRView for assigning the data from triple-resonance experiments.

The 5′-leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. Using a 2H-edited NMR approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (Core Encapsidation Signal; ΨCES). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing, and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.

SUMMARY Ligand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding. The conformation of the ligand, however, is generally presumed to have one primary binding mode, shifting the protein conformational ensemble from one state to another. We report solution NMR studies that reveal peroxisome proliferator-activated receptor γ (PPARγ) modulators can sample multiple binding modes manifesting in multiple receptor conformations in slow conformational exchange. Our NMR, hydrogen/deuterium exchange and docking studies reveal that ligand-induced receptor stabilization and binding mode occupancy correlate with the graded agonist response of the ligand. Our results suggest that ligand and receptor dynamics affect the graded transcriptional output of PPARγ modulators.