Receive a weekly summary and discussion of the top papers of the week by leading researchers in the field.

In Combinatorial chemistry & high throughput screening ; h5-index 0.0

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 is 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.

METHOD : Eight complexes are analyzed and molecular dynamics (MD) simulations are 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 -8.5kcal/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.

Rasool Nouman, Hussain Waqar

2019-Dec-13

DFT Analysis, GS-CA1, HIV-1 Capsid, Molecular Docking, Molecular Dynamics Simulation, Phosphorylation