Study summary · research use only
Electronic structure and physicochemical properties characterization of the amino acids 12-26 of TP53: a theoretical study
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This is a theoretical (computational chemistry) study, with no living organism involved. The authors examined PNC-27, a synthetic peptide derived from the TP53-HDM2 binding domain (TP53 residues 12-26) linked to a 17-amino-acid antennapedia transference domain, which they state induces membrane rupture in tumor cells through toroidal pore formation by an unknown mechanism. Using Hartree-Fock and density functional theory (B3LYP) calculations on TP53 residues 12-26 (PPLSQETFSDLWKLL), they characterized electronic structure and physicochemical properties. Charges fitted to the electrostatic potential indicated reactive sites (L14, S15, T18, S20, L25, and L26) potentially exposed to nucleophilic and electrophilic attack. The authors analyzed bond orders, intramolecular interactions, and global reactivity descriptors to characterize features they suggest may bear on the peptide's cancer-cell membrane lysis properties.
Abstract
PNC-27, a synthetic peptide, is derived from the TP53-HDM2 binding domain that include TP53 amino acids 12-26 linked with 17 amino acids from the antennapedia protein transference domain. This peptide induces membrane rupture in tumor cells through toroidal pores formation and has motivated several experimental studies; nonetheless, its mechanism of biological action remains unknown to date. Herein, we present a theoretical study at the Hartree-Fock and density functional theory (B3LYP) levels of theory of TP53 protein residues 12-26 (PPLSQETFSDLWKLL) in order to characterize its electronic structure and physicochemical properties. Our results for atomic and group charges, fitted to the electrostatic potential (ESP) show important reactive sites (L14, S15, T18, S20, L25, and L26), suggesting that these amino acids are exposed to nucleophilic and electrophilic attacks. Analysis of bond orders, intramolecular interactions and of several global reactivity descriptors, such as ionization potentials, hardness, electrophilicity index, dipole moments, total energies, frontier molecular orbitals (HOMO-LUMO), and electrostatic potential, led us to characterize active sites and the electronic structure and physiochemical features that taken together may be important in understanding the specific selectivity for this peptides type's cancer-cell membrane lysis properties.
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