Hi, I am looking to dock a database of ligands to a protein of interest.
The ligand database I have is excessively large and calculating partial charges and energy minimising will be unfeasible. Is it possible to run a pharmacophore query based on the receptor initially, and then energy minimize the hits followed by a docking simulation?
To me this seems problematic as pharmacophore query the shape of the pocket as part of the query. If ligands are not minimized, they may be in the incorrect orientation/shape.
Thanks.
Hi Christopher
First of all let me ask you about the software you are using for docking ?
The problem you have identified is absolutely correct. The whole idea of preparing the ligands is to generate various ionization states, Tautomers, stereo chemistry and ring conformation. Minimization of the ligand optimizes bond distances and angles to the quantum chemistry level calculation.
If you dont minimize the ligands, depending on the software, some of them might not even accept the ligands for docking.
I use Schrodinger for ligand preparation, and if you use a large database, the software automatically splits them in to different files. Once done, I use HTVS method for screening.
You are absolutely right but, one cannot escape from the database preparation prior to the pharmacophore mapping. Commercial software's are robust in doing this.
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