Identifying and Assessing Putative Allosteric Sites and Modulators for CXCR4 Predicted through Network Modeling and Site Identification by Ligand Competitive Saturation.

ABSTRACT: The chemokine receptor CXCR4 is a critical target for the treatment of several cancer types and HIV-1 infections. While orthosteric and allosteric modulators have been developed targeting its extracellular or transmembrane regions, the intramembrane region of CXCR4 may also include allosteric binding sites suitable for the development of allosteric drugs. To investigate this, we apply the Gaussian Network Model (GNM) to the monomeric and dimeric forms of CXCR4 to identify residues essential for its local and global motions located in the hinge regions of the protein. Residue interaction network (RIN) analysis suggests hub residues that participate in allosteric communication throughout the receptor. Mutual residues from the network models reside in regions with a high capacity to alter rec

SUBMITTER: Inan T 

PROVIDER: S-EPMC11139592 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature