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Screening and Docking

Recipe Generation

The first step of recipe generation is the identification and analysis of the target epitope. Typically, these targets should prioritize two elements: (i) structure stability and (ii) solvent exposure.

Stability is necessary in order to have a consistent target for the MIP cavity to form.

Exposure allows the functional monomers to dock and polymerize about the epitope to actually form the cavity.

Screening

# Screen using just GNINA/VINA
MIPkit -screen -template CD20-epitope.pdb

MIPkit -screen -template CD20-epitope.pdb -fms AAM NIPAM BIS AMPSA

# Screen using GNINA/VINA and GROMACS
MIPkit -gmxscreen -template CD20-epitope.pdb

MIPkit -gmxscreen -template CD20-epitope.pdb -fms AAM NIPAM BIS AMPSA

Following the selection of the epitope, all functional monomers present in ./constants/fm_list.yaml can be screened against the template using Autodock Vina or GNINA. Alternatively, -fms can be used to specify which functional monomers should be screened. Supported Functional Monomers contains a list of supported functional monomers for MIPkit, GNINA, and Vina. Docking method can be changed using -dockmethod.

-gmxscreen adds an additional interaction run to the docked FM and results in single FM H-bonds, energies, and RDF. This provides more insight into the template-FM interactions of the system, providing a better basis for recipe generation.

Precomplexation / Recursive Docking

MIPkit -dock -config CD20_MD.yaml

MIPkit -dock -template CD20-epitope.pdb -fms AAM 5 NIPAM 14 BIS 3 AMPSA 1

Precomplexes are formed by recursively docking functional monomers on the surface of the template. By default, the functional monomers are docked serially. In the above example, that means 5 AAM will be docked, followed by 14 NIPAM, then 3 BIS, and finally 1 AMPSA. More details on the differences this creates can be found in the CD20 Example. Alternatively, -shuffle can be used to randomize the structure.

-dock will determine the box shape based on the overall size of the template to perform blind docking. If you wish to restrict docking to a specific region, use a -config file with custom box dimensions. -dockmethod can be used to specify gnina or vina for docking and screening.