AMBER Archive (2002)

Subject: mm_pbsa positive binding energies

From: Mathy Froeyen (Matheus.Froeyen_at_rega.kuleuven.ac.be)
Date: Mon Sep 02 2002 - 04:11:34 CDT

Dear all,

We did some mm_pbsa calculations.

The resulting final free energy differences
are positive ( using the Poisson Boltzman (PB) option).

We expect negative dG values
because the binding of the ligand to the receptor
happens in the micromolar range.

We obtain similar results for other ligands.

We think that it has something to do with the fact that
our ligands are (-) charged and there are also counterions present
in the receptor.

All comments are very much appreciated.

best regards,
matheus froeyen

#####################################################
statistics.out
###############
                     complex
receptor ligand
ELE -9046.04 29.20 -8539.86 29.45
-107.86 2.84
VDW -707.32 26.04 -690.84 25.00
4.01 1.24
INT 4039.37 35.95 3979.00 35.94
60.36 4.58
GAS -5713.99 38.31 -5251.70 38.63
-43.48 5.09
PBSUR 46.30 0.42 47.55 0.42
1.54 0.01
PBCAL -2379.98 24.09 -2598.06 22.25
-305.65 2.52
PBSOL -2333.68 23.96 -2550.52 22.18
-304.10 2.51
PBELE -11426.02 24.76 -11137.93 20.92
-413.50 1.81
PBTOT -8047.67 36.86 -7802.21 34.91
-347.59 4.55
GBSUR 61.38 0.56 63.04 0.56
1.93 0.01
GB -1180.75 17.80 -1173.14 17.51
-238.37 2.92
GBSOL -1119.36 17.85 -1110.10 17.58
-236.44 2.92
GBELE -10226.79 29.35 -9713.00 28.55
-346.23 1.43
GBTOT -6833.36 37.37 -6361.80 36.95
-279.93 4.71

                    com - (rec + lig)
ELE -398.32 12.22
VDW -20.49 5.75
INT 0.00 0.00
GAS -418.81 11.23
PBSUR -2.79 0.08
PBCAL 523.73 15.50
PBSOL 520.94 15.49
PBELE 125.41 13.86
PBTOT 102.13 13.63
GBSUR -3.59 0.11
GB 230.76 10.47
GBSOL 227.18 10.46
GBELE -167.56 12.07
GBTOT -191.63 11.33

#################################################################
#
# 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 lig1_prot
PATH ../snapshots/
#
COMPLEX 1
RECEPTOR 1
LIGAND 1
#
COMPT ../com_parm.top
RECPT ../rec_parm.top
LIGPT ../lig_parm.top
#
GC 0
AS 0
DC 0
#
MM 1
GB 1
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 0.092
#
################################################################################

@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 /d2/sw/honig/release1_1/exe/delphi
#
################################################################################