Thank you very much STN.

I was not sure actually about MM-PBSA because in all the papers I have studied, researchers have applied 3D-RISM theory using AMBER package to calculate solvation free energy. I am not sure if MM-PBSA would serve the purpose because in it, the free energy of solvation is the energy required to transfer a solute from vacuum into the solvent. In the MM-PBSA approach, it is calculated using an implicit solvent model. In my case, I am treating explicit water as four point model. 

Hi, 

It's possible to use Justin's method for proteins. As he himself described it here : 

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/08_advanced.html

Just keep in mind to set  "couple-intramol' = no", If simulation crashes with "couple-intramol=no" then you have to do 2 calculations, first with  "couple-intramol=yes"  in water/solvent (DeltaG1) and second in protein in vacuum  (DeltaG2)  with "couple-intramol=yes" then subtract (DeltaG1 - DeltaG2) to obtain correct solvation energy.

Essentially, idea with "couple intramol= no" is that you don't want to decouple intramolecular bonds of protein. We are just interested in obtaining deltaG of protein and water interaction.      

Thank you very much @Vikas Dubey. I will try that.

Sorry to bump an old thread but how is it possible to simulate DeltaG2 in vaccum.

I get the box collapsing if I use NPT and using a different ensemble for G2 (i.e NVT) feels inconsistent?

Any help would be much appreciated

Hi Suniba Shuaib ,

Though I am late, but for a single structure solvation free energy can be calculated using a web server prowave (http://prowave.org/). You can extract a few strucutres from your trajectory and calculate dG. It can even decompose this value into residue wise solvation free energy.