Hi all,
Please suggest how I need to optimize a small molecule to generate the topology file for the ligand to process it for Protein-Ligand MD simulations.
I have tried to balance the valency of the molecule, after which I have submitted the molecule to CGenff server, but the charge penalty and penalty scores were very high.
After which I have tried to optimize the molecule using Avogadro software. Using the output from Avogadro, I have resubmitted the molecule to CGenff server, after which the penalty score was even higher.
I have also tried PRODRG and ATB but the molecule was broken in case of PRODRG, while processing for MD. The molecule contains 1 chlorine atom, also attaching the warning suggested by ATB server.
Kindly suggest how can I process this molecule? I am really new to this work. Please suggest if I am processing it appropriately or not.
Hi Pragya Anand ,
Does this molecule contain any metal atoms?, or is it an ion?
Looking at the optimized structure in the ATB, it doesn't appear to be in a minimized energy state. In addition, it has two heptagonal rings connected by a bridge. This type of chemical structure is unusual in molecular dynamics.
The correct solution is to parameterize these rings with CHARMM, or Gromos, or both.
Thank you for your suggestions. I will try CHARMM and GROMOS. The molecule only has non-metal elements. I have tried to minimize the structure using MD ensemble module of Chimera, but seems it didn't work.
It will be kind if you can elaborate on two heptagonal rings being not common in MD studies as I also have a pyranose structure?
If you molecule is not big you can optimize your structure using QM method.
Then supply your optimize structure into the Cgenff Server for the xyz.str file.
If you get again high penalty then you need to fit your penalty.
Hi Pragya Anand ,
I made a mistake, I'm sorry about that. There is only one ring with seven atoms, see Figure added. In general, force fields do not have parameters for structures that are not common. I'm assuming the indicated ring is correct.
Did you minimize the structure with all hydrogens explicitly? This procedure is mandatory.
Aashish Bhatt and Ranylson Marcello Leal Savedra I have tried to optimise the structure using Gaussian DFT but the output still showed high penalty score as before.
After adding hydrogens and minimizing the structure using MMFF94 using steepest descent method, then gave this file for DFT. But the penalty score is 258.
if you get high penalty score and you bond or angle or dihedral is very important for the interactions so you need to optimize your bond.
You can use FFParam software for bond fitting.
Thank you for your suggestions, Aashish Bhatt I was trying to approach this, but was stuck in the process of dependencies required to run FFParam. I will give it a go and will to optimize the structure.
If anyone can suggest a protocol, or articles to work with small molecules from basic levels to standard, where I can get the zest on how to apply force field for metal ion compounds and non-metallic compounds.
Hello Pragya Anand ,
If you can, share the PDB file of that chemical structure. Feel free to send it privately if you prefer.
It's a bit difficult to identify errors without the full messages and structures.
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