Validation of Protein Structure from Anisotropic Carbonyl Chemical Shifts in a Dilute Liquid Crystalline Phase. Study of conformational rearrangement and refinement of structural homology models by the use of heteronuclear dipolar couplings. A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles. Mapping of the binding interfaces of the proteins of the bacterial phosphotransferase system, HPr and IIAglc. Knowledge-Based Prediction of Protein Structures and the Design of Novel Molecules. On the combinatorial and algebraic complexity of quantifier elimination. An Improved Algorithm for Quantifier Elimination Over Real Closed Fields. The NOESY Jigsaw: automated protein secondary structure and main-chain assignment from sparse, unassigned NMR data. Validation of Protein Structure from Preparations of Encapsulated Proteins Dissolved in Low Viscosity Fluids. Acta Crystallogr B Biol Crystallogr 38 (1982), 778. The Structures of the Monoclinic and Orthorhombic Forms of Hen Egg-White Lysozyme at 6 Angstroms Resolution. Recognition of protein folds via dipolar couplings. Protein backbone structure determination using only residual dipolar couplings from one ordering medium. Towards Structural Genomics of RNA: Rapid NMR Resonance Assignment and Simultaneous RNA Tertiary Structure Determination Using Residual Dipolar Couplings. Finally, we extend NVR to a second application, 3D structural homology detection, and demonstrate that NVR is able to identify structural homologies between proteins with remote amino acid sequences using a database of structural models. We further demonstrate the feasibility of our algorithm for different and larger proteins, using NMR data for hen lysozyme (129 residues, 98% accuracy) and streptococcal protein G (56 residues, 95% accuracy), matched to a variety of 3D structural models. NVR achieves an average assignment accuracy of over 90%. The algorithm is demonstrated on NMR data from a 76-residue protein, human ubiquitin, matched to four structures, including one mutant (homolog), determined either by X-ray crystallography or by different NMR experiments (without RDCs). NVR runs in minutes and efficiently assigns the (H N, 15N) backbone resonances as well as the d NNs of the 3D \nfif-NOESY spectrum, in O(n 3) time. The algorithm requires only uniform 15N-labelling of the protein, and processes unassigned H N- 15N HSQC spectra, H N- 15N RDCs, and sparse H N-H N NOE's d NNs), all of which can be acquired in a fraction of the time needed to record the traditional suite of experiments used to perform resonance assignments. A new algorithm, called Nuclear Vector Replacement (NVR) is introduced to compute assignments that optimally correlate experimentally-measured NH residual dipolar couplings (RDCs) to a given a priori whole-protein 3D structural model. Assignments are also the starting point for structure determination and refinement. These assignments are a prerequisite for probing protein-protein interactions, protein-ligand binding, and dynamics by NMR. We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of an homologous structure. High-throughput NMR structural biology can play an important role in structural genomics.
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