Sandbox 645: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Ashraf Hasasneh, Tahreer Mutair, Charles Short

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 Currently there is no cure for HIV. However after some extensive research, some drugs were to be designed in order to pause the HIV affects. This happens by the ability of the drugs to mimic the tetrahedral intermediates in the active site and prevent the polypeptide from binding the Asp residues.
-, preventing the binding  of polyproteins. Its chemical structure mimics the tetrahedral intermediate of the hydrolytic reaction, thereby  <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'>interacting strongly with the catalytic Asp residues</scene>.<ref>PMID:17243183</ref> Saquinavir is essentially an uncleavable ligand, as indicated by the <scene name='User:David_Canner/Sandbox_HIV/Hiv_morph2/9'> similar conformational changes in the protease flaps </scene> on binding saquinavir or a polypeptide . Other drugs used to treat HIV infection that inhibit <scene name='User:David_Canner/Sandbox_HIV/Inhibitor_intro/1'>HIV protease</scene> include , , and .
 When a HIV virus infects an organism it tends to multiply within the body’s cells. The virus is then released to infect other cells. In this manner, the infection of HIV infects the newly made cells of the body. While the viruses are produced, proteins and enzymes used to manufacture the DNA in addition to other components of the virus are made.  In this case, protease is that enzyme that is needed to bring the structural and enzymes of the virus together. Protease drugs are what could inhibit this virus.
-*Design of a HIV-1 Protease inhibitor - Free-energy parameterization of enzyme-inhibitor binding.
+*Design of a <scene name='User:David_Canner/Sandbox_HIV/Inhibitor_intro/1'> HIV-1 Protease </scene> inhibitor - Free-energy parameterization of enzyme-inhibitor binding.
 Based on the crystal structure data and protein receptor ligand complexes studied, interatomic interactions that work on burying atoms and find the statistical preference for amino acid pairs. A free energy model of the receptor-ligand is formulated and helps in showing the interfacial interactions. The interaction strength of this model has a reliability of ±1.5 kcal/mol, which reveals the importance of atomic interaction to stabilize the receptor-ligand interface. The analysis of a binding motif of HIV-1 protease inhibitor complex shows the important contacts instead of the set of atoms.
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 *HIV Drugs:
-)	Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_tunnel/1'> tunnel tightly </scene>, which will prevent polyproteins from also binding.  Saquniavir's chemical structure has the ability to mimic the tetrahedral intermediate of the hydrolytic reaction to interact <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'> </scene>.[[Image:Saquin1.gif|frame|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]] Knowing that, Saquinavir is an uncleavable ligand by studying its similar conformational changes in binding saquinavir or a polypeptide. <ref>PMID: 20426757</ref> Two types of mutants can result as a way of depleting the effectiveness of the <scene name='User:David_Canner/Sandbox_HIV/Saquinavir/4'>Saquinavir</scene> ([[Invirase]]) drug. These mutants are G48V and G48V/L90M. They cause 13.5 and 149 fold reductions, respectively. Based on some quantum mechanical and molecular mechanical analysis of the interaction of the saquinavir interaction; a disturbance of the saquinavir with the mutant with a flap residue 48 leads to a change in the hydrogen bonding. This mutation leads to the loss in the inhibitor/ enzyme binding.
+)	Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_tunnel/1'> tunnel tightly </scene>, which will prevent polyproteins from also binding.  Saquniavir's chemical structure has the ability to <scene name='User:David_Canner/Sandbox_HIV/Hiv_morph2/9'> mimic the tetrahedral </scene>  intermediate of the hydrolytic reaction to interact <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'> strongly with the catalytic Asp residues</scene> <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'> </scene>.[[Image:Saquin1.gif|frame|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]] Knowing that, Saquinavir is an uncleavable ligand by studying its similar conformational changes in binding saquinavir or a polypeptide. <ref>PMID: 20426757</ref> Two types of mutants can result as a way of depleting the effectiveness of the <scene name='User:David_Canner/Sandbox_HIV/Saquinavir/4'>Saquinavir</scene> ([[Invirase]]) drug. These mutants are G48V and G48V/L90M. They cause 13.5 and 149 fold reductions, respectively. Based on some quantum mechanical and molecular mechanical analysis of the interaction of the saquinavir interaction; a disturbance of the saquinavir with the mutant with a flap residue 48 leads to a change in the hydrogen bonding. This mutation leads to the loss in the inhibitor/ enzyme binding.