Situating the Phosphonated Calixarene–Cytochrome C Association by Molecular Dynamics Simulations.

07 November 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Protein-calixarenes binding plays an increasing, 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 ap- proaches 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 struc- ture, the association has a larger structural impact in the protein dynamics. Our simulations, then, allow a direct comparison with analogous calixarenes, namely sulfonato, similarly re- ported 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.


molecular dynamics
cytochrome C
ab-initio dft

Supplementary materials

Supporting Information: Situating the Phosphonated Calixarene–Cytochrome C Association by Molecular Dynamics Simulations
Molecular dynamics simulations analysis: cluster analysis, distances, interacting angles, simulations setup, RMSD, salsa, rmsf


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.