Preferred drifting along the DNA major groove and cooperative anchoring of the p53 core domain: mechanisms and scenarios.

ABSTRACT: While the importance of specific p53-DNA binding is broadly accepted, the recognition process is still not fully understood. Figuring out the initial tetrameric p53-DNA association and the swift and cooperative search for specific binding sites is crucial for understanding the transactivation mechanism and selectivity. To gain insight into the p53-DNA binding process, here we have carried out explicit solvent molecular dynamic (MD) simulations of several p53 core domain-DNA conformations with the p53 and the DNA separated by varying distances. p53 approached the DNA, bound non-specifically, and quickly drifted along the DNA surface to find the major groove, cooperatively anchoring in a way similar to the specific binding observed in the crystal structure. Electrostatics was the major drivi

SUBMITTER: Pan Y 

PROVIDER: S-EPMC7316384 | biostudies-literature | 2010 Mar-Apr

REPOSITORIES: biostudies-literature