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Score bonus to hbond

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Score bonus to hbond

Hi all, 

I am trying to design a ligand binding protein. And I am just wondering is there any way to give bonus to the score when the protein is H-bonding to the ligand? Thank you all.

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Fri, 2019-07-05 12:28

There's some possibilities, though none are really directly straightforward.

One possibility is to use the ProteinLigandInterfaceUpweighter, which is a TaskOperation which causes the packer to add a bonus for protein-ligand interactions when doing design. It doesn't specifically increase the h-bonding weight, and only functions during fixed-backbone design in the packer, and not during minimization or other such stages of the full design protocol.

Another possibility assumes you have a specific hbonding interaction you can specify. In those cases you can write constraints which will recognize those hbonds, and will give a bonus for them. The downside here is that you would have to pre-specify the residues and atoms involved in the h-bonding interaction, and this is normally brittle to having those atoms always be present, so if you design those positions to non-hbonding residue types, Rosetta may crash on you.

A third possibility to look into is the HBNet code. This is specifically designed for creating hydrogen bonding networks. It doesn't necessarily simply give a bonus for good hydrogen bonds to a ligand, but it may allow you to design in hbonding interactions to the ligand.

A final possibility is to simply run design a bunch, and then use the presence of hydrogen bonders of the approriate type as a post-filter. You don't bonus the hydrogen bonds during the design run itself, but instead manually add in the bonus in your model selection step.

Tue, 2019-07-09 09:42