The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study
In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R2495 suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R2495 affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation Hi 68R on the R249S assists in maintaining the wild-type like flexibility of the U region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53. (C) 2010 Elsevier Ltd. All rights reserved.
p53-dna interaction ua-qcmd effect of mutation docking