The tumor suppressor protein p53 plays a central role in regulating cell cycle arrest, apoptosis, senescence, DNA repair, and metabolism, but ~55% of all human cancers are associated with mutations in p53, with over 90% of the mutations found in the DNA binding domain (DBD). Some peptides have been shown, experimentally, to restore the function of mutated p53, and bio-conjugation, especially aptamer-based, is a powerful tool for increasing the sensitivity and specificity of Raman spectroscopic identification of proteins in complex media. In this work molecular dynamics (MD) simulations are performed on various p53 and aptamer/peptide ligand docked conformations to identify the optimal combination for Raman studies. The p53 DBD and peptide structures are I-TASSER predicted conformations with covalent bonds for the ZN ion in p53 using ab-initio Density Functional Theory. The aptamer structures are RNAComposer predictions, and aptamer/peptide docking is performed with molecular docking tools. MD is performed using GROMACS packages over nanosecond time scales with ligand binding evaluation and root mean squared deviation analysis. The figure shows a predicted p53 structure with overlaid solvent exclusion surface before (Left) and after (Right) docking of an RNA aptamer ligand.

Molecular dynamics simulations of the p53 DNA-binding domain with RNA aptamer and peptide ligands to predict structural and dynamical features to explore and identify optimal conjugation ligands for spectroscopic investigations

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