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Comb Chem High Throughput Screen. 2019 Dec 13. doi: 10.2174/1386207323666191213142223. [Epub ahead of print]

Three Major Phosphoacceptor Sites in HIV-1 Capsid Protein Enhances its Structural Stability and Resistance against Inhibitor: Explication through Molecular Dynamics Simulation, Molecular Docking and DFT Analysis.

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Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270. Pakistan.
National Center of Artificial Intelligence, Punjab University College of Information Technology, University of the Punjab, Lahore. Pakistan.



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.


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.


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.


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).


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.


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

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