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Kinetic Computational Alanine Scanning: Application to p53 Oligomerization. Export

J Mol Biol (17 January 2006)

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computational oligomerization p53

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We have developed a novel computational alanine scanning approach that involves analysis of ensemble unfolding kinetics at high temperature to identify residues that are critical for the stability of a given protein. This approach has been applied to dimerization of the oligomerization domain (residues 326-355) of tumor suppressor p53. As validated by experimental results, our approach has reasonable success in identifying deleterious mutations, including mutations that have been linked to cancer. We discuss a method for determining the effect of mutations on the location of the dimerization transition state.


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