| A branch and bound algorithm for protein structure refinement from sparse NMR data sets. | |
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MedLine Citation:
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PMID: 9917406 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We describe new methods for predicting protein tertiary structures to low resolution given the specification of secondary structure and a limited set of long-range NMR distance constraints. The NMR data sets are derived from a realistic protocol involving completely deuterated 15N and 13C-labeled samples. A global optimization method, based upon a modification of the alphaBB (branch and bound) algorithm of Floudas and co-workers, is employed to minimize an objective function combining the NMR distance restraints with a residue-based protein folding potential containing hydrophobicity, excluded volume, and van der Waals interactions. To assess the efficacy of the new methodology, results are compared with benchmark calculations performed via the X-PLOR program of Brünger and co-workers using standard distance geometry/molecular dynamics (DGMD) calculations. Seven mixed alpha/beta proteins are examined, up to a size of 183 residues, which our methods are able to treat with a relatively modest computational effort, considering the size of the conformational space. In all cases, our new approach provides substantial improvement in root-mean-square deviation from the native structure over the DGMD results; in many cases, the DGMD results are qualitatively in error, whereas the new method uniformly produces high quality low-resolution structures. The DGMD structures, for example, are systematically non-compact, which probably results from the lack of a hydrophobic term in the X-PLOR energy function. These results are highly encouraging as to the possibility of developing computational/NMR protocols for accelerating structure determination in larger proteins, where data sets are often underconstrained. |
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Authors:
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D M Standley; V A Eyrich; A K Felts; R A Friesner; A E McDermott |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of molecular biology Volume: 285 ISSN: 0022-2836 ISO Abbreviation: J. Mol. Biol. Publication Date: 1999 Jan |
Date Detail:
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Created Date: 1999-03-01 Completed Date: 1999-03-01 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985088R Medline TA: J Mol Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1691-710 Citation Subset: IM |
Copyright Information:
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Copyright 1999 Academic Press. |
Affiliation:
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Department of Chemistry and Center for Biomolecular Simulation, Columbia University, New York, NY, 10027, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms* Databases, Factual Disulfides / chemistry Magnetic Resonance Spectroscopy* Models, Molecular Protein Conformation Proteins / chemistry* Thermodynamics |
| Grant Support | |
ID/Acronym/Agency:
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GM52018/GM/NIGMS NIH HHS; GM52091/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Disulfides; 0/Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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