overestimated dG values

[Aaron Jacob]

Greetings,

I have been trying to calculate delta G of binding of a antibody, antigen complex. But the dG values i get are extremely overestimated (-50 kcal/mol). Realistically speaking it should be around 10. how can i correct the estimation.

Below is the input file:

sys_name             = ""                                             
startframe           = 1                                              # First frame to analyze
endframe             = 9999999                                        # Last frame to analyze
interval             = 10                                              # Number of frames between adjacent frames analyzed
 forcefields          = "oldff/leaprc.ff99SB,leaprc.gaff"              # Define the force field to build the Amber topology
  ions_parameters      = 1                                              # Define ions parameters to build the Amber topology
  PBRadii              = 7                                              # Define PBRadii to build amber topology from GROMACS files
  temperature          = 298.15                                         # Temperature
  qh_entropy           = 0                                              # Do quasi-harmonic calculation
  interaction_entropy  = 0                                              # Do Interaction Entropy calculation
  ie_segment           = 25                                             # Trajectory segment to calculate interaction entropy
  c2_entropy           = 0                                              # Do C2 Entropy calculation
  assign_chainID       = 0                                              # Assign chains ID
  exp_ki               = 0.0                                            # Experimental Ki in nM
  full_traj            = 0                                              # Print a full traj. AND the thread trajectories
  gmx_path             = ""                                             # Force to use this path to get GROMACS executable
  keep_files           = 0                                              # How many files to keep after successful completion
  netcdf               = 0                                              # Use NetCDF intermediate trajectories
  solvated_trajectory  = 0                                              # Define if it is necessary to cleanup the trajectories
  verbose              = 1                                              # How many energy terms to print in the final output
/

# (AMBER) Possion-Boltzmann namelist variables
&pb
  ipb                  = 2                                              # Dielectric model for PB
  inp                  = 1                                              # Nonpolar solvation method
  sander_apbs          = 0                                              # Use sander.APBS?
  indi                 = 1.0                                            # Internal dielectric constant
  exdi                 = 80.0                                           # External dielectric constant
  emem                 = 4.0                                            # Membrane dielectric constant
  smoothopt            = 1                                              # Set up dielectric values for finite-difference grid edges that are located across the solute/solvent dielectric boundary
  istrng               = 0.15                                            # Ionic strength (M)
  radiopt              = 0                                              # Use optimized radii?
  prbrad               = 1.4                                            # Probe radius
  iprob                = 2.0                                            # Mobile ion probe radius (Angstroms) for ion accessible surface used to define the Stern layer
  sasopt               = 0                                              # Molecular surface in PB implict model
  arcres               = 0.25                                           # The resolution (Å) to compute solvent accessible arcs
  memopt               = 0                                              # Use PB optimization for membrane
  mprob                = 2.7                                            # Membrane probe radius in Å
  mthick               = 40.0                                           # Membrane thickness
  mctrdz               = 0.0                                            # Distance to offset membrane in Z direction
  poretype             = 1                                              # Use exclusion region for channel proteins
  npbopt               = 0                                              # Use NonLinear PB solver?
  solvopt              = 1                                              # Select iterative solver
  accept               = 0.001                                          # Sets the iteration convergence criterion (relative to the initial residue)
  linit                = 1000                                           # Number of SCF iterations
  fillratio            = 4.0                                            # Ratio between the longest dimension of the rectangular finite-difference grid and that of the solute
  scale                = 2.0                                            # 1/scale = grid spacing for the finite difference solver (default = 1/2 Å)
  nbuffer              = 0.0                                            # Sets how far away (in grid units) the boundary of the finite difference grid is away from the solute surface
  nfocus               = 2                                              # Electrostatic focusing calculation
  fscale               = 8                                              # Set the ratio between the coarse and fine grid spacings in an electrostatic focussing calculation
  npbgrid              = 1                                              # Sets how often the finite-difference grid is regenerated
  bcopt                = 5                                              # Boundary condition option
  eneopt               = 2                                              # Compute electrostatic energy and forces
  frcopt               = 0                                              # Output for computing electrostatic forces
  scalec               = 0                                              # Option to compute reaction field energy and forces
  cutfd                = 5.0                                            # Cutoff for finite-difference interactions
  cutnb                = 0.0                                            # Cutoff for nonbonded interations
  nsnba                = 1                                              # Sets how often atom-based pairlist is generated
  decompopt            = 2                                              # Option to select different decomposition schemes when INP = 2
  use_rmin             = 1                                              # The option to set up van der Waals radii
  sprob                = 0.557                                          # Solvent probe radius for SASA used to compute the dispersion term
  vprob                = 1.3                                            # Solvent probe radius for molecular volume (the volume enclosed by SASA)
  rhow_effect          = 1.129                                          # Effective water density used in the non-polar dispersion term calculation
  use_sav              = 1                                              # Use molecular volume (the volume enclosed by SASA) for cavity term calculation
  cavity_surften       = 0.0378                                         # Surface tension
  cavity_offset        = -0.5692                                        # Offset for nonpolar solvation calc
  maxsph               = 400                                            # Approximate number of dots to represent the maximum atomic solvent accessible surface
  maxarcdot            = 1500                                           # Number of dots used to store arc dots per atom
  npbverb              = 0                                              # Option to turn on verbose mode
/

[marioe911116]

Implicit solvent-based methods tend to overestimate the binding free energy significantly; it is a well-described fact in the literature. It's better to use them for relative comparisons rather than absolute ones

[Aaron Jacob]

Oh, I see.

Thank you for your kind reply

[Deepak Thakur]

First check the convergence of simulation (rmsd, rg, com distance......) and then try to apply mmpbsa on converged trajectory length.

--
You received this message because you are subscribed to the Google Groups "gmx_MMPBSA" group.
To unsubscribe from this group and stop receiving emails from it, send an email to gmx_mmpbsa+...@googlegroups.com.
To view this discussion visit https://groups.google.com/d/msgid/gmx_mmpbsa/6fac1c40-c69f-4a4d-977b-711f88cb2ce2n%40googlegroups.com.
For more options, visit https://groups.google.com/d/optout.