[AMBER] MMGBSA calculation gives very high positive free energy of binding!!!

From: Sandip Mondal <sandip_13.chem.iitkgp.ernet.in>
Date: Thu, 11 Jan 2018 15:11:12 +0530 (IST)

Hi all,
   I am a beginner of MMGBSA calculation. I tried to calculate the binding free energy between protein and DNA in one protein-DNA complex using MMGBSA method as implemented in Amber14. I have performed molecular dynamics simulation by NAMD using charmm force field. From there I have taken equilibrated trajectory for the analysis. So, in order to run MMGBSA script using NAMD generated files, I need the corresponding Amber topology files (.prmtop file) for complex (protein-DNA), receptor (protein), and ligand (DNA) seperately. Then I prepared the necessary .prmtop file by using CHAMBER tool. Here I used top_all27_prot_na.rtf and par_all27_prot_na.prm as topology and parameter files respectively (for protein as well as DNA) for the preparation of .prmtop files using CHAMBER conversion tool. After the preparation of all required files, I run MMGBSA script.

   During the calculation, I considered both multiple trajectory method as well as single trajectory method.

   In the result part for multiple trajectory method, I got very very high positive free energy change of binding between protein and DNA. One more thing, the bonded terms (bond, angle, dihedral) in the MMGBSA method shows very high value with respect to the bonded terms of NAMD log file.

   However for single trajectory method, the free energy of binding reduced around 1000 times but still it's high positive value.

   Indirectly these results suggest that the complex formation is unfavourable but in reality that protein-DNA complex exist.

   Can anybody please suggest what is my mistake?

   Any kind of suggestion is highly appreciable.

   Thanks in advance.


Sandip Mondal
Research Scholar
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Received on Thu Jan 11 2018 - 02:00:02 PST
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