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A procedure for the prediction of temperature-sensitive mutants of a globular protein based solely on the amino acid sequence

Varadarajan, Raghavan and Nagarajaram, HA and Ramakrishnan, C (1996) A procedure for the prediction of temperature-sensitive mutants of a globular protein based solely on the amino acid sequence. In: Proceedings of The National Academy of Sciences of The United States of America, 93 (24). pp. 13908-13913.

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Official URL: http://www.pnas.org/content/93/24/13908.abstract


Temperature-sensitive (Ts) mutants of a protein are an extremely powerful tool for studying protein function in vivo and in cell culture, We have devised a method to predict those residues in a protein sequence that, when appropriately mutated, are most likely to give rise to a Ts phenotype. Since substitutions of buried hydrophobic residues often result in significant destabilization of the protein, our method predicts those residues in the sequence that are likely to be buried in the protein structure, We also indicate a set of amino acid substitutions, which should be made to generate a Ts mutant of the protein. This method requires only the protein sequence, No structural information or homologous sequence information is required, This method was applied to a test data set of 30 nonhomologous protein structures from the Protein Data Bank, All of the residues predicted by the method to be greater than or equal to 95% buried were, in fact, buried in the protein crystal structure, In contrast, only 50% of all hydrophobic residues in this data set were greater than or equal to 95% buried, This method successfully predicts several known Ts and partially active mutants of T4 lysozyme, A repressor, gene V protein, and staphylococcal nuclease, This method also correctly predicts residues that form part of the hydrophobic cores of lambda repressor, myoglobin, and cytochrome b562

Item Type: Journal Article
Additional Information: Copyright of this article belongs to National Academy of Science.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Arun
Date Deposited: 08 Jan 2010 11:42
Last Modified: 19 Sep 2010 05:26
URI: http://eprints.iisc.ac.in/id/eprint/18990

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