Autodocking Studies of Oxygenated Fullerenes as HIV Protease Inhibitors in the Presence and in the Absence of Water
Type of Presentation
Paper
Location
University Library - D2401C
Start Date
4-17-2024 3:45 PM
End Date
4-17-2024 4:15 PM
Description of Program
In a previous study several oxygenated-fullerene compounds were shown to inhibit HIV protease (HIV-PR) with IC-50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The present study elucidates the mechanisms of the inhibition of HIV-PR by oxygenated-fullerenes by binding simulations using a molecular modeling software, AutoDock Vina.
Abstract
In a previous study several oxygenated fullerene compounds were produced by ozonation of C60 (Buckminsterfullerene) and were identified by elemental analysis and by SALI (surface analysis by laser ionization). Some of these compounds, especially a batch, SK-5, a mixture of C60O1-8, were shown to inhibit activities of HIV protease with IC-50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The oxygenated fullerenes were shown to have epoxide, ketones, and hydroxyl functionalities. The present study elucidates the mechanisms of the inhibition of HIV-PR by oxygenated fullerenes by binding simulations using a molecular modeling software, AutoDock Vina. The structures of C60O, C60O2, C60O3, C60O4, C60O5, C60O6, C60O7, C60O8 were generated using Spartan software and were docked with a crystal structure of the 5-CON HIV protease (HIV-PR) obtained from The Brookhaven Protein Data Bank using AutoDock Vina. These docking studies were done in the absence and presence of water, and showed that the oxygenated fullerenes bound to multiple sites of the HIV-PR with high binding affinities (-8.1 to -10.4kcal/mol). Nine docking poses were generated for each structure, and the models of each conformation were studied using PyMOL software. The docking models in PyMOL suggest that the high binding affinity is a result of the abundance of strong hydrogen bonds ~2.3Å long across the various C60OX structures, as well as the presence of dipole-dipole and van der Waals interactions, with several conformations exhibiting strong binding (≤9.8kcal/mol) with no hydrogen bonds.
Faculty / Staff Sponsor
Dr. Shailendra Kumar
Presentation File
wf_no
Autodocking Studies of Oxygenated Fullerenes as HIV Protease Inhibitors in the Presence and in the Absence of Water
University Library - D2401C
In a previous study several oxygenated fullerene compounds were produced by ozonation of C60 (Buckminsterfullerene) and were identified by elemental analysis and by SALI (surface analysis by laser ionization). Some of these compounds, especially a batch, SK-5, a mixture of C60O1-8, were shown to inhibit activities of HIV protease with IC-50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The oxygenated fullerenes were shown to have epoxide, ketones, and hydroxyl functionalities. The present study elucidates the mechanisms of the inhibition of HIV-PR by oxygenated fullerenes by binding simulations using a molecular modeling software, AutoDock Vina. The structures of C60O, C60O2, C60O3, C60O4, C60O5, C60O6, C60O7, C60O8 were generated using Spartan software and were docked with a crystal structure of the 5-CON HIV protease (HIV-PR) obtained from The Brookhaven Protein Data Bank using AutoDock Vina. These docking studies were done in the absence and presence of water, and showed that the oxygenated fullerenes bound to multiple sites of the HIV-PR with high binding affinities (-8.1 to -10.4kcal/mol). Nine docking poses were generated for each structure, and the models of each conformation were studied using PyMOL software. The docking models in PyMOL suggest that the high binding affinity is a result of the abundance of strong hydrogen bonds ~2.3Å long across the various C60OX structures, as well as the presence of dipole-dipole and van der Waals interactions, with several conformations exhibiting strong binding (≤9.8kcal/mol) with no hydrogen bonds.