search

fhh2626 / BFEE2

binding free energy estimator 2
GNU General Public License v3.0
102 stars 32 forks source link

Can a small DNA fragment be considered a ligand in BFEE #110

Open yasirmamun2088 opened 1 year ago

yasirmamun2088 commented 1 year ago

HelloProfessor, What I am trying to do is separate a small DNA fragment from the binding pocket of a protein and plot the free energy path. Should I use BFEE for this purpose, considering a DNA molecule has sidechain atoms and is more flexible than a small ligand?

Thank you so much Yasir

fhh2626 commented 9 months ago

Yes. You can do it if the DNA is not too large

yasirmamun2088 commented 9 months ago

Thank you for the reply. I have used bfee2 for my experiment since I wrote that comment. Unfortunately, I face some problems, especially with the r (detaching the ligand) part. First, the PMF merge did not work after I did the run in 5 windows. I decided to run it in a single window, but the ligand was pulled along with the protein, causing an unfolding-like event for the protein. And my delta G is abnormally high (-190 kcal/mol). I have added a picture of the simulation. I would appreciate any help.

bfee2-1 Thank you again.

fhh2626 commented 9 months ago

I am not sure what "the PMF merge did not work" mean. You can load a set of consecutive .czar.pmf files and merge them into one file. Alternatively, you can do it by hand.

Your system seems to large for molecular dynamics simulations. It is very difficult to converge. Maybe you can use a CG force field (e.g. SIRAH) to do the free-energy calculations.

yasirmamun2088 commented 8 months ago

Thank you for the reply and your suggestion, professor. I'm sorry, but I still have one question for you. When I add the consecutive .czar.pmf files and try to merge them using BFEE2Gui, it does not work; the files are not merged, and I get a file with only the results of the first file. This may be due to convergence issues. Can you give me any direction on how to do it by hand? Can I copy and paste the data for each file in one single file? I'll try to look into CG simulations as per your suggestion. Thanks again.

fhh2626 commented 8 months ago

Thank you for the reply and your suggestion, professor. I'm sorry, but I still have one question for you. When I add the consecutive .czar.pmf files and try to merge them using BFEE2Gui, it does not work; the files are not merged, and I get a file with only the results of the first file. This may be due to convergence issues. Can you give me any direction on how to do it by hand? Can I copy and paste the data for each file in one single file? I'll try to look into CG simulations as per your suggestion. Thanks again.

Please, check again whether you inputted consecutive .czar.pmf files. This issue is usually due to the .czar.pmf files are not consecutive