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HIV-1 Protease Molecular Docking and Molecular Dynamics Simulation

Molecular docking is a computational technique used to predict the binding mode of a ligand to a protein target. It is a crucial step in drug discovery, as it can help identify potential drug candidates. This repository contains files needed to perform molecular docking and molecular dynamics simulations on a dataset of ligands against a protein target. Around two thousand ligands were docked against the HIV-1 protease variant G48T/L89M protein (seen below).

HIV-1 protease variant G48T/L89M visualized wit hNGLView

HIV-1 protease is an enzyme that plays a crucial role in the replication of the human immunodeficiency virus (HIV). It cleaves the newly synthesized polyproteins into mature protein components of an HIV virion, the infectious form of a virus outside the host cell.

The docking was performed using QuickVina and the ligand with the best fit was selected for molecular dynamics simulation done using Gromacs. The simulation was carried a second time, this time with Saquinavir (seen below), a known inhibitor of the HIV-1 protease.

Saquinavir visualize with NGLView

Both simulations were compared in terms of their Root-Mean-Square Deviation (RMSD) and other properties to determine the quality of the fit and the potential of the new ligand as a drug candidate.

For more information, please refer to the report.

MD simulation visualization

Possible future work

  • Test mutated protease to see if the Saquinavir inhibitor binds.

References

  • QuickVina for molecular docking
  • Gromacs for MD simulations
  • NGLView for visualizations
  • RCSB to download HIV-1 protease variant G48T/L89M complexed with Saquinavir

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Molecular Docking and Molecular Dynamics Simulations of Ligands Against HIV-1 Protease

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