Team:Duke/Model/Docking
Docking of Monomeric and Homodimeric Griffithsin
Protein-Ligand Docking overview
Docking is a molecular modeling method used to predict the interactions between proteins and small molecule ligands. After predicting the thermostability of GRFT variants using YASARA, we must make sure our thermoengineered structures retain their biological activity. Although we preserved the binding loops of the two proteins, we will determine the binding activity of our proteins by comparing the locations and relatives stabilities of small molecule docking of the normal and engineered variants. Through the use of ZDOCK, a docking software platform used to predict the top 20,000 interactions between small molecules and proteins, we will create structures used for quantitative and qualitative analysis. We predict the thermostable variants will have the same topology of binding to Gp120 and HIV/Zika antibodies since only a few amino acids in the non-binding loop region were altered.
The docking of gp120, a viral glycoprotein formed once the protease of a host cell processes the HIV 1 envelope, will be useful in understanding how to construct the lateral flow assay using GRFT. Since gp120 will be the analyte of interest, useful in immobilizing blood cells infected with HIV, we must ensure that our engineered variants readily bind to gp120 and the specific HIV and Zika antibodies.
Gp120 Griffithsin protein docking
Both the non-thermostable and thermoengineered GRFT monomer docked with Gp120 at the same binding sites shown above
Both the non-thermostable and thermoengineered GRFT homodimer docked with Gp120 at the same binding sites shown above
Homodimeric GRFT HIV Antibody Docking Results
The image above shows the docked thermostable homodimer with gp120 and HIV antibody 5TE4. The binding loop was intact and the structural integrity was preserved. The two subunits of the GRFT are colored magenta and cyan, while the antibody is colored green.
The image above shows the docked thermostable homodimer with gp120 and HIV antibody 5HM1. The secondary structure was not destroyed and the interactions between the small molecules are just as stable as those in the non-thermostabe homodimeric analog. The two subunits of the GRFT are colored magenta and cyan, while the antibody is colored red.
Monomeric GRFT Zika Antibody Docking Results
The image above shows the docked thermostable monomeric GRFT with gp120 and the Zika antibody 5KVG. The docked superstructure was stable and the structural integrity was preserved. The GRFT subunit is cyan and the antibody is colored green.
