I have a flexible docking related issue that I was hoping someone might have a solution for.
Many of my compounds have amidinium functional groups. I would like to model the positive charge as being delocalized over the two nitrogens and carbon. If I model the compound using partial double bonds, CHARMm seems to type the molecule and add charges correctly. However, when I try to do flexible docking, I get an message saying "No docking poses found." If I model my amidinium without any partial bonds (i.e. modelling a single resonance structure with a neutral nitrogen and a nitrogen with a formal +1 charge), the docking simulation runs fine and finds a great deal of docked poses. It seems that one can't input a molecule with partial double bonds into a docking simulation (aromatic bonds on the phenyl rings work fine, however). Is there any way around this? Is there a ways to assign custom charges to the atoms (I was thinking to reassign the CHARMm charges from the delocalized structure to the single resonance structure)? I've tried inspecting the atoms and changing the partial charges there, but that causes the docking simulation to not find any poses.
Thanks!
Scott Johnson
Houk Lab
UCLA
Many of my compounds have amidinium functional groups. I would like to model the positive charge as being delocalized over the two nitrogens and carbon. If I model the compound using partial double bonds, CHARMm seems to type the molecule and add charges correctly. However, when I try to do flexible docking, I get an message saying "No docking poses found." If I model my amidinium without any partial bonds (i.e. modelling a single resonance structure with a neutral nitrogen and a nitrogen with a formal +1 charge), the docking simulation runs fine and finds a great deal of docked poses. It seems that one can't input a molecule with partial double bonds into a docking simulation (aromatic bonds on the phenyl rings work fine, however). Is there any way around this? Is there a ways to assign custom charges to the atoms (I was thinking to reassign the CHARMm charges from the delocalized structure to the single resonance structure)? I've tried inspecting the atoms and changing the partial charges there, but that causes the docking simulation to not find any poses.
Thanks!
Scott Johnson
Houk Lab
UCLA
