AMBER Archive (2002)

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

From: Giulio Rastelli (rastelli.giulio_at_unimo.it)
Date: Wed Oct 09 2002 - 13:04:10 CDT

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
-------------------------------------