Back to Search Start Over

Situating the phosphonated calixarene–cytochrome C association by molecular dynamics simulations.

Authors :
Bartocci, Alessio
Dumont, Elise
Source :
Journal of Chemical Physics. 3/14/2024, Vol. 160 Issue 10, p1-11. 11p.
Publication Year :
2024

Abstract

Protein–calixarenes binding plays an increasingly central role in many applications, spanning from molecular recognition to drug delivery strategies and protein inhibition. These ligands obey a specific bio-supramolecular chemistry, which can be revealed by computational approaches, such as molecular dynamics simulations. In this paper, we rely on all-atom, explicit-solvent molecular dynamics simulations to capture the electrostatically driven association of a phosphonated calix-[4]-arene with cytochome-C, which critically relies on surface-exposed paired lysines. Beyond two binding sites identified in direct agreement with the x-ray structure, the association has a larger structural impact on the protein dynamics. Then, our simulations allow a direct comparison to analogous calixarenes, namely, sulfonato, similarly reported as "molecular glue." Our work can contribute to a robust in silico predictive tool to assess binding sites for any given protein of interest for crystallization, with the specificity of a macromolecular cage whose endo/exo orientation plays a role in the binding. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219606
Volume :
160
Issue :
10
Database :
Academic Search Index
Journal :
Journal of Chemical Physics
Publication Type :
Academic Journal
Accession number :
176035982
Full Text :
https://doi.org/10.1063/5.0198522