Background: Human Immunodeficiency Virus 1 (HIV-1) is a lentivirus, which causes various HIV-associated infections. The HIV-1 core dissociation is essential for viral cDNA synthesis and phosphorylation of HIV-1 capsid protein (HIV-1 CA) plays an important role in it.
Objective: The aim of this study was to explicate the role of three phosphoserine sites i.e. Ser109, Ser149 and Ser178 in the structural stability of HIV-1 CA, and it’s binding with GS-CA1, a novel potent inhibitor.
Methods: Eight complexes were analyzed and Molecular Dynamics (MD) simulations were performed to observe the stability of HIV-1 CA in the presence and absence of phosphorylation of serine residues at four different temperatures i.e. 300K, 325K, 340K and 350K, along with molecular docking and DFT analysis.
Results: The structures showed maximum stability in the presence of phosphorylated serine residue. However, GS-CA1 docked most strongly with the native structure of HIV-1 CA i.e. binding affinity was -8.5 kcal/mol (Ki = 0.579 µM).
Conclusion: These results suggest that the phosphorylation of these three serine residues weakens the binding of GS-CA1 with CA and casts derogatory effect on inhibition potential of this inhibitor, but it supports the stability of HIV-1 CA structure that can enhance regulation and replication of HIV-1 in host cells.
[http://dx.doi.org/10.3390/ijms19051436] [PMID: 29751616]
[http://dx.doi.org/10.1074/jbc.274.27.19434] [PMID: 10383459]
[http://dx.doi.org/10.1371/journal.ppat.1006441] [PMID: 28683086]
[http://dx.doi.org/10.1016/j.jmb.2007.07.070] [PMID: 17826792]
[http://dx.doi.org/10.1038/nature12769] [PMID: 24196705]
[http://dx.doi.org/10.1128/AAC.00985-13] [PMID: 23817385]
[http://dx.doi.org/10.1016/j.jmb.2008.02.066] [PMID: 18374356]
[http://dx.doi.org/10.1186/s12977-016-0262-0] [PMID: 27107820]
[http://dx.doi.org/10.1128/JVI.02155-16] [PMID: 28202766]
[http://dx.doi.org/10.1128/AAC.02574-15] [PMID: 26810656]
[http://dx.doi.org/10.1093/jac/dkx208] [PMID: 29091184]
[http://dx.doi.org/10.1021/jp973084f] [PMID: 24889800]
[http://dx.doi.org/10.1016/j.compbiolchem.2017.04.005] [PMID: 28552695]