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Structural Point Mutations of p53 Protein and Their Effects on the Zinc Coordination Complex
Author(s) -
Quinn Taylor,
Thayer Kelly
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.712.23
Subject(s) - point mutation , molecular dynamics , biology , biophysics , mutation , p53 protein , protein structure , protein stability , protein–protein interaction , chemistry , genetics , computational biology , microbiology and biotechnology , biochemistry , gene , computational chemistry
The p53 protein is an important transcription factor in the cell cycle. As such, mutations of this protein are found in at least 50% of all cancers, most of which are in the DNA‐binding domain containing residues 102‐292. This research is focusing on the molecular dynamics of p53 with point mutations that affect the structural stability of the protein, namely, R175H, R282W, G245S, and R249S. The system will be evaluated in reference to the Zn 2+ cation that is tetrahedrally coordinated to Cys176, Cys238, Cys242, and His179. Changes in the stability of the coordination complex have been shown to have a greater effect on the stability of the overall protein, as it restricts the movement of the L2 and L3 loops. These systems and their changes are evaluated using molecular dynamic simulations with the AMBER12 suite, cpptraj, VMD and PyMOL. The objective of this study is to investigate how point mutations change the structural stability of the protein in relation to the zinc complex. Structural metrics including distance and surface measures shed light of the effects of these mutations on the dynamics of the protein. This informs future research initiatives for rational drug design.