Computational geometry: an introduction
Computational geometry: an introduction
A new method for modeling and solving the protein fold recognition problem (extended abstract)
RECOMB '98 Proceedings of the second annual international conference on Computational molecular biology
Extracting structural information using time-frequency analysis of protein NMR data
RECOMB '01 Proceedings of the fifth annual international conference on Computational biology
Computing in Science and Engineering
Large a polynomial-time nuclear vector replacement algorithm for automated NMR resonance assignments
RECOMB '03 Proceedings of the seventh annual international conference on Research in computational molecular biology
3D Structural Homology Detection via Unassigned Residual Dipolar Couplings
CSB '03 Proceedings of the IEEE Computer Society Conference on Bioinformatics
High-Throughput 3D Structural Homology Detection via NMR Resonance Assignment
CSB '04 Proceedings of the 2004 IEEE Computational Systems Bioinformatics Conference
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It is well known that the NMR method for protein structure determination applies to small proteins and that its effectiveness decreases very rapidly as the molecular weight increases beyond about 30 kD. We have recently developed a method for protein structure determination that can fully utilize partial NMR data as calculation constraints. The core of the method is a threading algorithm that guarantees to find a globally optimal alignment between a query sequence and a template structure, under distance constraints specified by NMR/NOE data. Our preliminary tests have demonstrated that a small number of NMR/NOE distance restraints can significantly improve threading performance in both fold recognition and threading-alignment accuracy, and can possibly extend threading's scope of applicability from structural homologs to structural analogs. An accurate backbone structure generated by NMR-constrained threading can then provide a significant amount of structural information, equivalent to that provided by the NMR method with many NMR/NOE restraints; and hence can greatly reduce the amount of NMR data typically required for accurate structure determination. Our prelimenary study suggest that a small number of NOE restraints may suffice to determine adequately the all-atom structure when those restraints are incorporated in a procedure combining threading, modeling of loops and sidechains, and molecular dynamics simulation. Potentially, this new technique can expand NMR's capability to larger proteins.