title: Relative Stability of Wild-Type and Mutant p53 Core Domain: A Molecular Dynamic Study.
abstract: The p53 protein is a stress response protein that functions primarily as a tetrameric transcription factor. A tumor suppressor p53 binds to a specific DNA sequence and transactivates target genes, leading to cell cycle apoptosis. Encoded by the human gene TP53, p53 is a stress response protein that functions primarily as a tetrameric transcription factor. This gene regulates a large number of genes in response to a variety of cellular functions, including oncogene activation and DNA damage. Mutations in p53 are common in human cancer types. Herein we mutate a wild-type p53, 1TSR with four of its mutated proteins. The energy for the wild-type and mutated proteins is calculated by using molecular dynamics simulations along with simulated annealing. Our results show significant differences in energy between hotspot mutations and the wild type. Based on the findings, we investigate the correlation between molar masses of the target residue and the relative energy with respect to the wild type. Our results indicate that the relative energy changes play a pivotal role in bioactivity, in conformity with observations in the rate of mutation in biology.
authors.affiliation: 1 Department of Physics and Center for Functional Nanoscale Materials, Clark Atlanta University , Atlanta, Georgia .
authors.forename: Leyla
authors.initials: L
authors.lastname: Rohani
authors.affiliation: 2 Department of Biology, Center for Cancer Research and Therapeutics Development, Clark Atlanta University , Atlanta, Georgia .
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Morton
authors.affiliation: 1 Department of Physics and Center for Functional Nanoscale Materials, Clark Atlanta University , Atlanta, Georgia .
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: 2 Department of Biology, Center for Cancer Research and Therapeutics Development, Clark Atlanta University , Atlanta, Georgia .
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
keywords: 1TSR; CHARMM; core domain; mutations; p53; simulation