--pharma vs --template

[okbckim]

Hi there

Can explain what --pharma option does? I find --template option will bias docking toward pharmacophore defined in ph4 file. But I cannot find how --pharma option work. Any example can also help.

Thank you very much

[biocheming]

Actually, the --template option is indeed used for docking based on a pharmacophore (a pharmacophore template, with shape[defined by heavy atoms]). In addtiion, the grid energy used during docking is derived from this pharmacophore template. During the conformational search, both the global search and local optimization are based on this grid energy.

On the other hand, the --pharma option also allows you to input a pharmacophore, but when using only --pharma, the grid energy is still based on the interaction between the ligand and the protein. The results of --pharma can only serve as rewards or penalties, because this input does not determine the grid energy or the forces on ligand atoms.

However, --pharma does have an advantage. During high-throughput virtual screening, if you provide one or two key pharmacophore features, it can be used to filter the results. Using the --ph4_cutoff option, the output can retain only conformations with the critical pharmacophore features. Additionally, during the conformational search, it will focus on conformations that match the key features defined by --pharma, and conformations that do not align with the --pharma definition will be filtered more quickly.

Moreover, pharmacophores can be generated based on known receptor-ligand interactions by using the --genph4 option.

[okbckim]

Thank you for the clarification! All make sense now.