Solving systems of polynomial inequalities in subexponential time
Journal of Symbolic Computation
Complexity of deciding Tarski algebra
Journal of Symbolic Computation
On the combinatorial and algebraic complexity of quantifier elimination
Journal of the ACM (JACM)
Matrix computations (3rd ed.)
Protein structure determination using protein threading and sparse NMR data (extended abstract)
RECOMB '00 Proceedings of the fourth annual international conference on Computational molecular biology
An Improved Algorithm for Quantifier Elimination Over Real Closed Fields
FOCS '97 Proceedings of the 38th Annual Symposium on Foundations of Computer Science
3D Structural Homology Detection via Unassigned Residual Dipolar Couplings
CSB '03 Proceedings of the IEEE Computer Society Conference on Bioinformatics
Protein similarity from knot theory and geometric convolution
RECOMB '04 Proceedings of the eighth annual international conference on Resaerch in computational molecular biology
High-Throughput 3D Structural Homology Detection via NMR Resonance Assignment
CSB '04 Proceedings of the 2004 IEEE Computational Systems Bioinformatics Conference
CISA: Combined NMR Resonance Connectivity Information Determination and Sequential Assignment
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
A markov random field framework for protein side-chain resonance assignment
RECOMB'10 Proceedings of the 14th Annual international conference on Research in Computational Molecular Biology
RIBRA–an error-tolerant algorithm for the NMR backbone assignment problem
RECOMB'05 Proceedings of the 9th Annual international conference on Research in Computational Molecular Biology
A Tabu Search Approach for the NMR Protein Structure-Based Assignment Problem
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
Proceedings of the 15th annual conference companion on Genetic and evolutionary computation
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High-throughput NMR structural biology can play an important role in structural genomics. We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of an homologous structure. These assignments are a prerequisite for probing protein-protein interactions, protein-ligand binding, and dynamics by NMR. Assignments are also the starting point for structure determination and refinement. 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. The algorithm requires only uniform 15N-labelling of the protein, and processes unassigned HN-15N HSQC spectra, HN-15N RDCs, and sparse HN-HN NOE's dNNs), 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. NVR runs in minutes and efficiently assigns the (HN,15N) backbone resonances as well as the dNNs of the 3D \nfif-NOESY spectrum, in O(n3) time. 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 achieves an average assignment accuracy of over 90%. 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. 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.