Molecular Dynamics Simulation Study of the HIV-1 Protease Inhibit ion Using Fullerene and New Fullerene Derivatives of Carbon Nanostructures.
BACKGROUND
The water insolubility of fullerene C60 nanostructure greatly hampers its biological applications as an effective HIV-1 protease inhibitor, which suggests to synthesis new C60 derivatives with different functional polar groups.


METHODS
The new carbon nanostructures of fulleropyrrolidines with one and two polar acetoxyhydroxyl (AcH) groups (C60-A and C60-B, respectively) were constructed to evaluate their interactions and binding affinity into HIV-1 protease active site via theoretical molecular docking and molecular dynamic simulations. Data obviously indicated the higher affinity of fulleropyrrolidines derivatives C60-A and C60-B compared to fullerene C60 in interacting with HIV-1 protease active site cavity. The functional groups in C60 caused better residing of C60 derivatives in the center of active site by changing the spherical shape of C60, constructing different stable H-bonds with supporting the main π interactions between C60 and aromatic Phe53/Arg8 in protease active site. Our finding showed that the functionalization of C60 is essential for both increasing solubility and improving different π interactions of C60 with protease. Also, H-bond forming with AcH functional groups and enzyme active site residues is more important to support the van der Waals interactions between C60 fragment of fulleropyrrolidines and enzyme cavity. Since enzyme possesses aspartic acid residues in active site, C60-B with two AcH groups interacted with the active site more efficiently via additional H-bond relative to C60-A.


RESULTS
Finally, the results indicate a possible use of the investigated fulleropyrrolidines derivatives as new HIV-1 protease inhibitors.
Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran.
Abolfazl
A
Barzegar
Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran.
Esmail
E
Naghizadeh
Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran.
Mostafa
M
Zakariazadeh
Department of Chemistry, University of Tabriz, Tabriz, Iran.
Jafar
J
Azamat
D002244:Carbon / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007477:Ions / Q000737:chemistry / Q000494:pharmacology; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D013329:Structure-Activity Relationship
D037741:Fullerenes; D017320:HIV Protease Inhibitors; D007477:Ions; D002244:Carbon; D016333:HIV Protease
AIDS; HIV-1 protease; fullerene; fulleropyrrolidine; molecular docking; molecular dynamic