Two molecular dynamics simulations of the region E17-N29 of p53 (p53 17-29) at different temperatures were performed for a total time of 0.2 μs, to study the conformational landscape of this region. Previous studies have suggested that this region displays different structural motifs, such as helix of a double β-turn, and that its secondary structure might be transiently stable. Interestingly, in this study it was found that the region F19-L25, and particularly its fragment F19-L22, display a stable, transient helical pattern at sub-microsecond periods. The region F19-L22, which contains one of the most important residues needed for the interaction of p53 with MDM2, seems to be formed and stabilized by the existence of one hydrophobic and one aromatic cluster. The main function of these clusters is to help their surrounding area to desolvate, to allow the hydrogen bond network, therefore favoring the formation of a stable helix. This preliminary study would be useful for a better understanding of the structure and function of the N-terminal domain of p53 and its implications for the control of different types of cancer.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Apr 28 2006|
Bibliographical noteFunding Information:
L.M.E.F would like to thank David D. Thomas for his support and encouragement. The authors’ research was supported by supercomputing time granted by the Minnesota Supercomputing Institute, University of Minnesota to L.M.E.F. and by grants from CONACYT and CGPI-IPN to J.G.T.F.
Copyright 2008 Elsevier B.V., All rights reserved.
- Molecular dynamics simulations
- N-terminal domain
- p53-MDM2 interaction