Paper Info
Title
Theoretical studies on the interactions and interferences of HIV-1 glycoprotein gp120 and its coreceptor CCR5.
Abstract
The interaction between the HIV gp120 protein and coreceptor CCR5 or CXCR4 of the host cell is critical in mediating the HIV entry process. A model for the CCR5-gp120 complex has been developed. In the model, the N-terminus of CCR5 binds to three discontinuous domains of gp120, including the fourth conserved (C4) region, β19/β20 connecting loop, and V3 loop. The second extra-cellular loop (ECL2) of CCR5 also interacts with the crown part of the gp120 V3 loop. The bindings of the three CCR5 antagonists, maraviroc, aplaviroc, and vicriviroc, to the trans-membrane domain of CCR5 have been modeled. The bindings are found to affect the conformation of the ECL2 domain, which in turn drives the N-terminus of CCR5 to an altered state. Aplaviroc is more hydrophilic than maraviroc and vicriviroc, and its binding is more interfered by solvent, resulting in a quite different effect to the structure of CCR5 compared with those of the other two molecules. The above results are in accord with experimental observations and provide a structural basis for further design of CCR5 antagonists.
Year
DOI
Venue
2011
10.1021/ci1003448
Journal of Chemical Information and Modeling
Keywords
DocType
Volume
IMMUNODEFICIENCY-VIRUS TYPE-1,CHEMOKINE RECEPTOR CCR5,AMINO-TERMINAL DOMAIN,MOLECULAR-DYNAMICS SIMULATION,PROTEIN-COUPLED RECEPTOR,2ND EXTRACELLULAR LOOP,D-PEPTIDE INHIBITORS,PARTICLE MESH EWALD,ENVELOPE GLYCOPROTEIN,ENTRY INHIBITOR
Journal
51
Issue
ISSN
Citations 
2
1549-960X
0
PageRank 
References 
Authors
0.34
0
2
Name
Order
Citations
PageRank
Lin-tai Da101.69
Yun-Dong Wu283.43