2ppz: Difference between revisions
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'''NMR solution Structure of the Villin Headpiece Mutant G34L'''<br /> | '''NMR solution Structure of the Villin Headpiece Mutant G34L'''<br /> | ||
==Overview== | |||
BACKGROUND: As a rule, peptides are more flexible and unstructured than proteins with their substantial stabilizing hydrophobic cores. Nevertheless, a few stably folding peptides have been discovered. This raises the question whether there may be more such peptides that are unknown as yet. These molecules could be helpful in basic research and medicine. RESULTS: As a method to explore the space of conformationally stable peptides, we have developed an evolutionary algorithm that allows optimization of sequences with respect to several criteria simultaneously, for instance stability, accessibility of arbitrary parts of the peptide, etc. In a proof-of-concept experiment we have perturbed the sequence of the peptide Villin Headpiece, known to be stable in vitro. Starting from the perturbed sequence we applied our algorithm to optimize peptide stability and accessibility of a loop. Unexpectedly, two clusters of sequences were generated in this way that, according to our criteria, should form structures with higher stability than the wild-type. The structures in one of the clusters possess a fold that markedly differs from the native fold of Villin Headpiece. One of the mutants predicted to be stable was selected for synthesis, its molecular 3D-structure was characterized by nuclear magnetic resonance spectroscopy, and its stability was measured by circular dichroism. Predicted structure and stability were in good agreement with experiment. Eight other sequences and structures, including five with a non-native fold are provided as bona fide predictions. CONCLUSION: The results suggest that much more conformationally stable peptides may exist than are known so far, and that small fold classes could comprise well-separated sub-folds. | |||
==About this Structure== | ==About this Structure== | ||
2PPZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PPZ OCA]. | 2PPZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PPZ OCA]. | ||
==Reference== | |||
Evolutionary Pareto-optimization of stably folding peptides., Gronwald W, Hohm T, Hoffmann D, BMC Bioinformatics. 2008 Feb 19;9:109. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18284690 18284690] | |||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gronwald, W.]] | [[Category: Gronwald, W.]] | ||
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[[Category: in silico sequence optimization]] | [[Category: in silico sequence optimization]] | ||
[[Category: small stable core]] | [[Category: small stable core]] | ||
[[Category: structural protein]] | |||
[[Category: thermostable]] | [[Category: thermostable]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:43:06 2008'' | ||
Revision as of 10:43, 14 March 2008
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NMR solution Structure of the Villin Headpiece Mutant G34L
OverviewOverview
BACKGROUND: As a rule, peptides are more flexible and unstructured than proteins with their substantial stabilizing hydrophobic cores. Nevertheless, a few stably folding peptides have been discovered. This raises the question whether there may be more such peptides that are unknown as yet. These molecules could be helpful in basic research and medicine. RESULTS: As a method to explore the space of conformationally stable peptides, we have developed an evolutionary algorithm that allows optimization of sequences with respect to several criteria simultaneously, for instance stability, accessibility of arbitrary parts of the peptide, etc. In a proof-of-concept experiment we have perturbed the sequence of the peptide Villin Headpiece, known to be stable in vitro. Starting from the perturbed sequence we applied our algorithm to optimize peptide stability and accessibility of a loop. Unexpectedly, two clusters of sequences were generated in this way that, according to our criteria, should form structures with higher stability than the wild-type. The structures in one of the clusters possess a fold that markedly differs from the native fold of Villin Headpiece. One of the mutants predicted to be stable was selected for synthesis, its molecular 3D-structure was characterized by nuclear magnetic resonance spectroscopy, and its stability was measured by circular dichroism. Predicted structure and stability were in good agreement with experiment. Eight other sequences and structures, including five with a non-native fold are provided as bona fide predictions. CONCLUSION: The results suggest that much more conformationally stable peptides may exist than are known so far, and that small fold classes could comprise well-separated sub-folds.
About this StructureAbout this Structure
2PPZ is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Evolutionary Pareto-optimization of stably folding peptides., Gronwald W, Hohm T, Hoffmann D, BMC Bioinformatics. 2008 Feb 19;9:109. PMID:18284690
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