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Homologs of the tumor suppressor protein p53: A bioinformatics study for drug design

MOJ Proteomics & Bioinformatics
Kelly M Thayer, Claudia Carcamo

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Sequence and structure of proteins related to the tumor suppressor protein p53 were studied from  the  perspective  of  gaining  insight  for  the  development  of  therapeutic  drugs.  Our  study  addresses  two  major  issues  encumber  bringing  novel  drugs  to  market:  side  effects  and artifacts from animal models. In the first phase of our study, we performed a genome-wide  search  to  identify  potentially  similar  proteins  to  p53  that  may  be  susceptible  to  off  target effects. In the second phase, we chose a selection of common model organisms that could  potentially  be  available  to  undergraduate  researchers  in  the  university  setting  to  assess which ones utilize p53 most similar to humans on the basis of sequence homology and structural similarity from predicted structures. Our results confirm the proteins in the humans significantly similar to p53 are known paralogs within the p53 family. In considering model organisms, murine p53 bore great similarity to human p53 in terms of both sequence and structure, but others performed similarly well. We discuss the findings against the background of other structural benchmarks and point out potential benefits and drawbacks of various alternatives for use in future drug design pilot studies.


protein p53, cancer, projections, influence, human tumors