On the allosteric puzzle and pocket crosstalk through computational means

Allostery is a constitutive, albeit often elusive, feature of biomolecular systems, which heavily determines their functioning. Its mechanical, entropic, long-range, ligand, and environment-dependent nature creates far from trivial interplays between residues and, in general, the secondary structure...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of chemical physics 2023-04, Vol.158 (16)
Main Authors: Aguti, Riccardo, Bernetti, Mattia, Bosio, Stefano, Decherchi, Sergio, Cavalli, Andrea
Format: Article
Language:English
Subjects:
Allosteric Regulation
Allosteric Site
Crosstalk
Kinases
Protein Structure, Secondary
Proteins - chemistry
Receptors
Residues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Allostery is a constitutive, albeit often elusive, feature of biomolecular systems, which heavily determines their functioning. Its mechanical, entropic, long-range, ligand, and environment-dependent nature creates far from trivial interplays between residues and, in general, the secondary structure of proteins. This intricate scenario is mirrored in computational terms as different notions of “correlation” among residues and pockets can lead to different conclusions and outcomes. In this article, we put on a common ground and challenge three computational approaches for the correlation estimation task and apply them to three diverse targets of pharmaceutical interest: the androgen A2A receptor, the androgen receptor, and the EGFR kinase domain. Results show that partial results consensus can be attained, yet different notions lead to pointing the attention to different pockets and communications.
ISSN:0021-9606
1089-7690
DOI:10.1063/5.0145364