Computational protocol: Epitope Mapping of M36, a Human Antibody Domain with Potent and Broad HIV-1 Inhibitory Activity

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Protocol publication

[…] Discovery Studio 3.5 (DS 3.5, Accelrys Software Inc., San Diego, CA) Modeler block was used to construct a homology model of m36. Heavy chain coordinates from antibodies with PDB codes 3E0T, 2NZ9, and 2GCY were used as templates for structure alignments to produce m36 homology models. All the 3 CDR loops in the m36 VH domain model were identified against antibody database, and reconstructed using the Model Antibody Loops protocol and subjected to Loops refinement protocol in DS 3.5. The final VH model was validated by using Ramachandran plot and Verify protein (Profiles-3D) protocol.For protein-ligand docking, 3D structure of gp120 (PDB code: 2NXY) was retrieved from the PDB and initialized as receptor molecules with the DS 3.5 tool “Protein Preparation”. All the possible torsion angles in ligand molecules (m36) were set to rotate freely. The flexible molecular docking of m36 VH onto gp120 model was accomplished using ZDOCK protocol in DS 3.5 with high predictive accuracy Generic Algorithm (GA) parameters. For each gp120 ligand, ten ligand poses were generated from docking experiment and evaluated with ZDOCK score function taking into account factors such as H-bonding energy, van der Waals energy and ligand torsion strain. The ligand poses with ZDOCK score above 11 were refined and analyzed using Rdock in DS 3.5. The top ranked ligand poses for gp120 were used for further study. The molecular interactions between m36 and gp120 were analyzed using the program “Protein Interface Analysis”. […]

Pipeline specifications

Software tools ZDOCK, rDock
Application Protein interaction analysis
Organisms Human immunodeficiency virus 1