Binding free energy (polar and nonpolar solvation energy)

[Nitin Sharma]

Hello Nathan,

I have been through lot of threads dealing with binding free energy calculations and APBS. My objective is to calculate binding free energy using MMPBSA for protein-ligand complex.

ΔGbind = ΔGcomplex - ΔGprotein  - ΔGligand  

ΔG(x) = Emm(x) + Gsolvation(x) - TΔS

 OR

ΔG(x) = Gpolar(x) + Gapolar(x)  + Gsolvation(x) - TΔS

Now, if we are taking same protein with different ligands we can disregard entropy contributions can be neglected if only a comparison of states of similar entropy is desired such as two ligands binding to the same protein is required.

So, ΔG(x) = Gpolar(x) + Gapolar(x)  + Gsolvation(x)

Now 

Gsolvation = (Complex_sol - Comp_ref) - (protein_sol - protein_ref) - (Ligand_sol - Ligand_ref)

Gpolar = (Complex_polar - Comp_ref) - (protein_polar - protein_ref) - (Ligand_polar - Ligand_ref)

Gsolvation = [(Complex_apolar - Comp_ref) + (pV + γA)] - [(Complex_apolar - Comp_ref) + (pV + γA)] - [(Complex_apolar - Comp_ref) + (pV + γA)]

* So how do we calculate pV + γA 

File for solvation energy is:

read
   mol pqr ion.pqr
 end
 elec name solv # Electrostatics calculation on the solvated state
         mg-manual 
         dime 97 97 97 
         nlev 4 
         grid 0.33 0.33 0.33 
         gcent mol 1 
         mol 1 
         lpbe 
         bcfl mdh 
         pdie 1.0 
         sdie 78.54 
         chgm spl2 
         srfm mol 
         srad 1.4 
         swin 0.3 
         sdens 10.0 
         gamma 0.14
         temp 298.15 
         calcenergy total 
         calcforce no 
         write pot dx potential
 end
   elec name ref # Calculate potential for reference (vacuum) state
         mg-manual
         dime 97 97 97
         nlev 4
         grid 0.33 0.33 0.33
         gcent mol 1
         mol 1
         lpbe
         bcfl mdh
         pdie 1.0
         sdie 1.0
         chgm spl2
         srfm mol
         srad 1.4
         swin 0.3
         sdens 10.0
         gamma 0.14
         temp 298.15
         calcenergy total
         calcforce no
 end
 # Calculate solvation energy
 print energy solv - ref end
 quit

WHAT WILL BE THE PARAMETERS FOR THE REFERENCE FILE OF NON POLAR CALCULATIONS

File for nonpolar energy is:

read
   mol pqr 2minimize_2HU4_laninamivir_superimposed_b.pqr
end

 apolar name solv 
     grid 0.3 0.3 0.3
  mol 1
  srfm mol
  swin 0.3
  srad 0.65
  press 0.2394
  gamma 0.0085
  bconc 0.033428
  sdens 100.0
  dpos 0.2
  temp 298.15
  calcenergy total
  calcforce no

end
apolar name ref # Calculate potential for reference (vacuum) state
    bconc
    dpos
    gamma
    grid
    mol 1
	press
    sdens 
    srad 
    srfm mol       
    swin       
    temp 298.15
    calcenergy total
    calcforce no
end
   # Calculate solvation apolEnergy
   print apolEnergy solv - ref end
   quit

ALSO WHAT DIFFERENCE WILL BE BETWEEN THE PARAMETERS OF SOLVATION FILE AND POLAR SOLVATION FILE 

Waiting for reply.

Thanks in advance,

Nitin