AMBER Archive (2002)

Subject: Re: reaction field energy of a ligand in MM-PBSA

From: Lepsa (lepsik_at_marilyn.uochb.cas.cz)
Date: Wed Oct 09 2002 - 08:19:56 CDT

Dear Giulio,
you have to edit crg file to put in charges for the inhibitor atoms.

Regards,

Martin Lepsik

> Dear all,
> I have run MD of a protein-ligand complex in a box of water, and I am
> analyzing
> free energies using MM-PBSA. I found that the reaction-filed energy of
> the ligand itself is zero, while the corresponding energies are non-zero
> for the complex.
> I believe it should not be ZERO. Now, my question is how Delphi can
> calculate the
> electrostatic component of solvation if the charges of the ligand are
> not present
> in my_amber94_delphi.crg file (there are only AA charges in this file);
> are these taken from the amber topology file?
> The input files follow, thank you very much for your help.
> Giulio
>
> ####mm_pbsa.in
> #
> # Input parameters for mm_pbsa.pl
> #
> # Holger Gohlke
> # 08.02.2002
> #
>
############################################################################
####
> @GENERAL
> #
> # General parameters
> # 0: means NO; >0: means YES
> #
> # mm_pbsa allows to calculate (absolute) free energies for one
> molecular
> # species or a free energy difference according to Receptor + Ligand
> = Complex,
> # DeltaG = G(Complex) - G(Receptor) - G(Ligand).
> #
> # PREFIX - To the prefix, "{_com, _rec, _lig}.crd.Number" is added
> during
> # generation of snapshots as well as during mm_pbsa
> calculations.
> # PATH - Specifies the location where to store or get snapshots.
> # COMPLEX - Set to 1 if free energy difference is calculated.
> # RECEPTOR - Set to 1 if either (absolute) free energy or free energy
> difference
> # are calculated.
> # LIGAND - Set to 1 if free energy difference is calculated.
> #
> # COMPT - Name of the parmtop file for the complex (not necessary for
> option GC).
> # RECPT - Name of the parmtop file for the receptor (not necessary for
> option GC).
> # LIGPT - Name of the parmtop file for the ligand (not necessary for
> option GC).
> #
> # GC - Snapshots are generated from trajectories (see below).
> # AS - Residues are mutated during generation of snapshots from
> trajectories.
> # DC - Decompose the free energies in single contributions (only works
> with MM and GB yet).
> #
> # MM - Calculation of gasphase energies using sander.
> # GB - Calculation of desolvation free energies using the GB models in
> sander (see below).
> # PB - Calculation of desolvation free energies using delphi (see
> below).
> # MS - Calculation of nonpolar contributions to desolvation using
> molsurf (see below).
> # If MS == 0, nonpolar contributions are calculated with the LCPO
> method in sander.
> # NM - Calculation of entropies with nmode.
> #
> PREFIX geld
> PATH ./
> #
> COMPLEX 1
> RECEPTOR 0
> LIGAND 0
> #
> COMPT geld.top
> RECPT
> LIGPT
> #
> GC 0
> AS 0
> DC 0
> #
> MM 1
> GB 0
> PB 1
> MS 1
> #
> NM 0
> #
>
############################################################################
####
> @DELPHI
> #
> # Delphi parameters
> #
> # The first group of the following parameters are passed to delphi.
> # Additional parameters (e.g. SALT) may be added here.
> # For further details see the delphi documentation.
> #
> # FOCUS - If FOCUS > 0, subsequent (multiple) PERFIL and SCALE
> parameters are
> # used for multiple delphi calculations using the focussing
> technique.
> # The # of _focussing_ delphi calculations thereby equals the value
> of FOCUS.
> # INDI - Dielectricity constant for the molecule.
> # EXDI - Dielectricity constant for the surrounding solvent.
> # PERFIL - Percentage of the lattice that the largest linear dimension
> of the
> # molecule will fill.
> # SCALE - Lattice spacing in no. of grids per Angstrom.
> # LINIT - No. of iterations with linear PB equation.
> # BNDCON - Type of boundary condition.
> # CHARGE - Name of the charge file.
> # SIZE - Name of the size (radii) file.
> #
> # SURFTEN / SURFOFF - Values used to compute the nonpolar contribution
> Gnp to the
> # desolvation according to Gnp = SURFTEN * SASA +
> SURFOFF.
> #
> FOCUS 0
> INDI 1.0
> EXDI 80.0
> PERFIL 80.0
> SCALE 2
> LINIT 1000
> BNDCON 4
> CHARGE ./my_amber94_delphi.crg
> SIZE ./my_parse_delphi.siz
> #
> SURFTEN 0.00542
> SURFOFF 0.92
> #
>
############################################################################
####
> @GB
> #
> # GB parameters
> #
> # The first group of the following parameters are passed to sander.
> # For further details see the sander documentation.
> #
> # IGB - Switches between Tsui's GB (1), Onufriev's GB (2),
> # Jayaram's et al. GB (3) or Jayaram's et al. MGB (4).
> # SALTCON - Concentration (in M) of 1-1 mobile counterions in
> solution.
> # EXTDIEL - Dielectricity constant for the surrounding solvent.
> #
> # SURFTEN / SURFOFF - Values used to compute the nonpolar contribution
> Gnp to the
> # desolvation according to Gnp = SURFTEN * SASA +
> SURFOFF.
> #
> IGB 4
> SALTCON 0.00
> EXTDIEL 80.0
> #
> SURFTEN 0.0072
> SURFOFF 0.00
> #
>
############################################################################
####
> @MS
> #
> # Molsurf parameters
> #
> # PROBE - Radius of the probe sphere used to calculate the SAS.
> # RADII - Name of the radii file.
> #
> PROBE 1.4
> RADII ./atmtypenumbers
> #
>
############################################################################
#####
> @PROGRAMS
> #
> # Program executables and paths
> #
> DELPHI /utenti/giulio/DELPHI/delphi
> #
>
############################################################################
####
>
>
> #####Statistics file:
> # MEAN STD
> # =======================
> ELE -74.67 1.95
> VDW 8.55 3.17
> INT 98.06 4.89
> GAS 31.93 4.02
> PBSUR 3.44 0.03
> PBCAL 0.00 0.00
> PBSOL 3.44 0.03
> PBELE -74.67 1.95
> PBTOT 35.38 4.02
>
>
> #######
> --
>
> Giulio Rastelli
> Dipartimento di Scienze Farmaceutiche
> Universita di Modena e Reggio Emilia
> Via Campi 183
> 41100 Modena - ITALY
> -------------------------------------
> tel 0039-059-2055145
> fax 0039-059-2055131
> -------------------------------------