Analysis of the bonding affinities between human PSGL-1 and Vpu derived from the different HIV-1 groups - in silico...

Human P-selectin glycoprotein ligand 1 (PSGL-1) and HIV-1 viral protein U (Vpu) play major roles in limiting and increasing the ability of HIV-1 to infect cells, respectively. There is currently no published data reporting on the specific interactions between PSGL-1 and Vpu, and possible outcomes and consequences of these interactions. To date, it has only been established that Vpu binds human PSGL-1 to degrade PSGL-1 and therefore promote HIV replication. There are, however, four different types of HIV-1, and it would be helpful to know how VpuM, VpuN, VpuO, and VpuP can bind to and possibly inhibit PSGL-1 expression. Bioinformatics methods were used to find out how strongly each type of Vpu found in the different HIV-1 groups bonds with human PSGL-1. Thus, we used molecular docking (MD) and molecular dynamics simulations (MDS) to figure out how PSGL-1 and VpuM, VpuN, VpuO, and VpuP interact with each other. To ensure the reliability of the predicted outcomes, the binding energy of each model was calculated using the MM/GBSA technique. Our findings show that PSGL-1-VpuP (4 H bonds, 2 salt bridges) and PSGL-1-VpuM (3 H bonds, 2 salt bridges) have stronger bonding affinities than PSGL-1-VpuN (4 H bonds, no salt bridges) and PSGL-1-VpuO (2 H bonds, 1 salt bridge). The MDS test also shows that PSGL-1-VpuM and PSGL-1-VpuP protein complexes are more stable and compact, with lower residual fluctuations compared to PSGL-1-VpuN and PSGL-1-VpuO protein complexes. Binding free energies of -82.27 ± 1.35 kcal/mol, -82.17 ± 0.84 kcal/mol, -67.84 ± 0.63 kcal/mol, and -131.86 ± 1.08 kcal/mol were recorded for each of PSGL1-VpuM, PSGL1-VpuN, PSGL1-VpuO, and PSGL1-VpuP, respectively, which further supports our results. Our research shows that Vpu from the M and P HIV-1 groups may be better at blocking human PSGL-1 than VpuO and VpuN groups. These results are novel in this specific realm of HIV research, and as such, further investigations in more robust experimental studies are warranted.