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
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.