Infinite polar contribution to binding energy MM-PBSA

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1

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Dear GROMACS users,
after MD simulations of a protein interacting with a graphene, I ran the g_mmpbsa analyses in order to obtain the binding free energy between protein and graphene. The overall charge of the protein is -7 and thus it is compensated by the presence of 7 Na+ cations.

The enthalpy contribution of the gaseous phase and the nonpolar contribution to the binding free energy look reasonably. Anyway, when I ran the analysis of the polar contribution using the following parameters in the polar.mdp file

;Polar calculation: “yes” or “no”
polar = yes

;=============
;PSIZE options
;=============
;Factor by which to expand molecular dimensions to get coarsegrid dimensions.
cfac = 1.5

;The desired fine mesh spacing (in A)
gridspace = 0.5

:Amount (in A) to add to molecular dimensions to get fine grid dimensions.
fadd = 5

;Maximum memory (in MB) available per-processor for a calculation.
gmemceil = 4000

;=============================================
;APBS kwywords for polar solvation calculation
;=============================================
;Charge of positive ions
pcharge = 1

;Radius of positive charged ions
prad = 0.95

;Concentration of positive charged ions
pconc = 0.150

;Charge of negative ions
ncharge = -1

;Radius of negative charged ions
nrad = 1.81

;Concentration of negative charged ions
nconc = 0.150

;Solute dielectric constant
pdie = 2

;Solvent dielectric constant
sdie = 80

;Reference or vacuum dielectric constant
vdie = 1

;Solvent probe radius
srad = 1.4

;Method used to map biomolecular charges on grid. chgm = spl0 or spl2 or spl4
chgm = spl4

;Model used to construct dielectric and ionic boundary. srfm = smol or spl2 or spl4
srfm = smol

;Value for cubic spline window. Only used in case of srfm = spl2 or spl4.
swin = 0.30

;Numebr of grid point per A^2. Not used when (srad = 0.0) or (srfm = spl2 or spl4)
sdens = 10

;Temperature in K
temp = 310

;Type of boundary condition to solve PB equation. bcfl = zero or sdh or mdh or focus or map
bcfl = mdh

;Non-linear (npbe) or linear (lpbe) PB equation to solve
PBsolver = lpbe

the analysis failed with the following error message

NOsh: Deprecated use of ION keyword! Use key-value pairs

and with the following contents in io.mc file

PMG: iteration = 40
PMG: relative residual = nan
PMG: contraction number = nan

I have looked at a tutorial with some sample files and I have noticed that there were no counterions considered in the xtc file in spite of the non-zero overall charge of the protein. I would like to ask whether I should skip the sodium cations and consider only the protein and whether the error message is associated with the presence of counterions in my xtc file.

Thank you for your answer in advance

Greetings

Zuzana

2

Topic- Regarding high negative polar solvation energy.

Dear gromacs users,
My question is something similar.

I have calculated the binding free energy between a nanoparticle surface and protein by g_mmpbsa method. The polar solvation energy is coming out to be negative and approximately -1162.248 kJ/mol due to this the total binding energy is highly negative approximately -2289.345 kJ/mol.

According to me this much of energy is not acceptable ideally I think.

I have checked all the possible reasons and changed parameters of the input file. My simulation length is also very long.

Please suggest me something. What could be the reason behind negative polar solvation energy and is this energy is acceptable.

Kindly suggest me something. I shall be very thankful to all of you.

Thank you in advance.

3

Why do you arrive at this conclusion? Binding energies between large species may be huge.

4

Dear sir thank you for your kind reply.

I draw this conclusion based on the literature. I have gone through a lot of papers in which they were calculated binding free energy between protein and nanoparticle surface (for exp. CNT, graphene, fullerenes and BNNTs).
In most of the studies the polar solvation energy is coming out to be positive because of solvation effect. It works for unbinding. But in my case it is highly negative. That’s why I was thinking maybe my calculations are wrong somewhere.

Please correct me if I understand the explanation wrong.

I shall be very thankful.

5

Each of those systems has different properties, and often CNT are treated as uncharged (LJ only) so naturally the magnitudes of polar solvation energy will be different. I have seen lots of really weird values come out of g_mmpbsa but have never used it so I can’t comment directly. It’s not an official GROMACS program so you may want to inquire with its author about specific odd outcomes.

6

Thank you very much for your suggestions.