Homologs of the Tumor Suppressor Protein p53: A Bioinformatics Study for Drug Design.

Abstract

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.