Acta Phys. -Chim. Sin. ›› 2012, Vol. 28 ›› Issue (07): 1665-1675.doi: 10.3866/PKU.WHXB201204182

• THEORETICAL AND COMPUTATIONAL CHEMISTRY • Previous Articles     Next Articles

Effects of the Residue Mutations on the Segment of P53-DNA Binding Region Based on Molecular Dynamics Simulation

XU Zhao-Ying1,3, ZHAO Li-Ling1,2, CAO Zan-Xia1,2, WANG Ji-Hua1,2   

  1. 1. Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics (Dezhou University), Dezhou 253023, Shandong Province, P. R. China;
    2. Department of Physics, Dezhou University, Dezhou 253023, Shandong Province, P. R. China;
    3. College of Physics and Electronics, Shandong Normal University, Jinan 250014, P. R. China
  • Received:2012-01-10 Revised:2012-04-14 Published:2012-06-07
  • Contact: WANG Ji-Hua E-mail:jhwyh@yahoo.com.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (30970561, 31000324) and Natural Science Foundation of Shandong Province, China (2009ZRA14027, 2009ZRA14028).

Abstract:

The structural characteristics of the peptide segment of the P53-DNA binding domain (from residue 230 to 258) were studied using molecular dynamics simulations with different mutations, including R249S, R248W, and G245S. Four independent simulations, including the wild-type segment wtP53, onepoint mutation segment P53-R249S, two-point mutation segment P53-R249S/R248W, and three-point mutation segment P53-R249S/R248W/G245S, were performed using the GROMACS software package and GROMOS 43A1 force field. Each simulation was run for 500 ns. The results indicated that mutation R249S affected the formation of the secondary structure for some residues, but had little impact on the mode of the ternary structure and made the segment more stable than the wild-type segment. In contrast, the R249S/R248W mutation strengthened the effect of R249S on the segment and induced a significant change in the ternary structure, with the structure of the two-point mutation segment R249S/R248W existing as a double-turn motif and becoming more stable. Moreover, the G245S mutation had the opposite effect on the segment, decreasing or eliminating entirely the effects caused by the R249S/R248W mutation on the segment. This study provided important understanding of the molecular mechanism of tumorigenesis and the design of a new drug.

Key words: P53 protein, Residue mutation, Structural change, Molecular dynamics simulation, Structure heterogeneity

MSC2000: 

  • O643