Hi,
I am planning to study the mechanism of drug efflux membrane protein using MD simulations. I have successfully docked the ligand. Now I would like to perform MD simulations on the protein. Regarding this I have a few queries:
1. Should the protein alone or the protein-ligand complex should be minimized?
2. Which force field should I select for simulation? I am planning to use NAMD through VMD as I am new to the field of MD simulations.
3. The protein is known to anti-port H+ along with the drug ligand. How can I include protons and parameters for this?
4. How long should I run the simulation to find the intermediate states of ligand efflux?
Please provide the links of any papers or protocols studying the similar processes.
Thank you.
Hi, fist of all most of these questions should be answered by you, you can not and should not try to find exact answers for your research by others. In any case:
1. You could try both scenarios to verify if you get accepted energy values after minimisation. If so, continue with either one or pick what it's best for your system.
2. Try to look at literature for any similar work. Which ff do they choose, for what reasons? Also take a look at the ffs' papers to see what they offer and for what systems are better suited for.
3. Usually software like Gromacs/Maestro do this job for you. Keep in mind that you should always check - inspect your system after each part.
4. In order to be as sure as possible find from literature (similar work) what simulation times they used.
You can start working with these, if you have any trouble in the future the community is always happy to help.
As you have mentioned you are new to MD Simulation and your background is microbiology. So I'll suggest you to use charmm-gui for insertion of protein in membrane. It'll be easy for you. For membrane proteins I usually prefer Charmm36 or Amber FF. You may face problem for analysis after simulation as all the analysis in NAMD are through scripting. I'm not discouraging you for using NAMD. It's really interesting tool, but for beginner like you may face problem during analysis as it'll need lot of programming skill. Therefore I'll recommend you to use Gromacs as for you it'll be easy to handle for analysis. In gromacs there are ready-made analysis tools which you can do easily. Based upon your system size and computational resources do simulation.
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