Dear all,
I have used mm_pb(gb)sa (pbsa module of amber) method to calculate the binding fre energy of 3 protein-protein complexes. The snapshots were taken at every 20 ps for a total of 2 ns (100 snapshots). I am sure that all the snapshots are taken from equilibrium state. The results of pbsa and gbsa are seem to be consistent with each other for two complexes but are very inconsistent. I have used the default parameter settings and same surften/surfoff values. I also applied the masterbug.fix. Below are the mm_pbsa.in and statistics.out files. I could not figure out why the gbsa and pbsa results are so different for one of the cases.
Thanks in advance.
Aytug
#
# Input parameters for mm_pbsa.pl
#
# Holger Gohlke
# 08.01.2002
#
################################################################################
.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 - parmtop file for the complex (not necessary for option GC).
# RECPT - parmtop file for the receptor (not necessary for option GC).
# LIGPT - 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 into individual contributions
# (only works with MM and GB).
#
# MM - Calculation of gas phase 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 ss
PATH ../snapshots3
#
COMPLEX 1
RECEPTOR 1
LIGAND 1
#
COMPT ../../common/sspbsa.prmtop
RECPT ../../common/sschainApbsa.prmtop
LIGPT ../../common/sschainBpbsa.prmtop
#
GC 0
AS 0
DC 0
#
MM 1
GB 1
PB 1
MS 0
#
NM 0
#
################################################################################
.PB
#
# PB parameters (this section is only relevant if PB = 1 above)
#
# The following parameters are passed to the PB solver.
# Additional parameters (e.g. SALT) may be added here.
# For further details see the delphi and pbsa documentation.
#
# PROC - Determines which method is used for solving the PB equation:
# If PROC = 1, the delphi program is applied. If PROC = 2,
# the pbsa program of the AMBER suite is used.
# REFE - Determines which reference state is taken for PB calc:
# If REFE = 0, reaction field energy is calculated with EXDI/INDI.
# Here, INDI must agree with DIELC from MM part.
# If REFE > 0 && INDI > 1.0, the difference of total energies for
# combinations EXDI,INDI and 1.0,INDI is calculated.
# The electrostatic contribution is NOT taken from sander here.
# INDI - Dielectric constant for the molecule.
# EXDI - Dielectric constant for the surrounding solvent.
# SCALE - Lattice spacing in no. of grids per Angstrom.
# LINIT - No. of iterations with linear PB equation.
# PRBRAD - Solvent probe radius in A (e.g. use 1.4 with the PARSE parameter set
# and 1.6 with the radii optimized by R. Luo)
#
# Parameters for pbsa only
#
# RADIOPT - Option to set up atomic avity radii for molecular surface calculation
# and dielectric assignment. A value of 0 uses the cavity radii from the prmtop file.
# A value of 1 sets up optimized cavity radii at the pbsa initialization phase.
# The latter radii are optimized for model compounds of proteins only; use cautions
# when applying these radii to nucleic acids.
#
# Parameters for delphi only
#
# 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 thus equals the value of FOCUS.
# PERFIL - Percentage of the lattice that the largest linear dimension of the
# molecule will fill.
# 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.
#
#
PROC 2
REFE 0
INDI 1.0
EXDI 80.0
SCALE 2.0
LINIT 1000
PRBRAD 1.4
#
RADIOPT 0
#
#FOCUS 0
#PERFIL 80.0
#CHARGE ./my_amber94_delphi.crg
#SIZE ./my_parse_delphi.siz
#
SURFTEN 0.005
SURFOFF 0.0
#
################################################################################
.MM
#
# MM parameters (this section is only relevant if MM = 1 above)
#
# The following parameters are passed to sander.
# For further details see the sander documentation.
#
# DIELC - Dielectricity constant for electrostatic interactions.
# Note: This is not related to GB calculations.
#
DIELC 1.0
#
################################################################################
.GB
#
# GB parameters (this section is only relevant if GB = 1 above)
#
# 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, 5).
# GBSA - Switches between LCPO (1) and ICOSA (2) method for SASA calc.
# Decomposition only works with ICOSA.
# SALTCON - Concentration (in M) of 1-1 mobile counterions in solution.
# EXTDIEL - Dielectricity constant for the solvent.
# INTDIEL - Dielectricity constant for the solute
#
# SURFTEN / SURFOFF - Values used to compute the nonpolar contribution Gnp to
# the desolvation according to Gnp = SURFTEN * SASA + SURFOFF.
#
IGB 1
GBSA 2
SALTCON 0.00
EXTDIEL 80.0
INTDIEL 1.0
#
SURFTEN 0.005
SURFOFF 0.0
#
################################################################################
.MS
#
# Molsurf parameters (this section is only relevant if MS = 1 above)
#
# PROBE - Radius of the probe sphere used to calculate the SAS.
# Since Bondi radii are already augmented by 1.4A, PROBE should be 0.0
#
PROBE 0.0
#
#################################################################################
.PROGRAMS
#
# Program executables
#
DELPHI /home/gohlke/src/delphi.98/exe/delphi
#
################################################################################
Compex 1 There is an inconsistency between PBSA and GBSA
# COMPLEX RECEPTOR LIGAND
# ----------------------- ----------------------- -----------------------
# MEAN STD MEAN STD MEAN STD
# ======================= ======================= =======================
ELE -25633.53 159.14 -12823.37 127.79 -12580.78 97.30
VDW -3962.18 42.43 -1951.69 31.23 -1902.47 27.68
INT 14798.11 73.79 7414.17 53.25 7383.93 56.72
GAS -14797.59 168.93 -7360.89 128.37 -7099.32 106.08
PBSUR 194.44 1.29 101.84 1.00 106.24 0.66
PBCAL -9834.42 147.56 -4955.06 118.15 -5221.96 89.07
PBSOL -9639.98 146.95 -4853.22 117.53 -5115.72 88.91
PBELE -35467.95 83.26 -17778.43 58.03 -17802.74 61.49
PBTOT -24437.58 105.57 -12214.10 71.99 -12215.04 74.55
GBSUR 194.44 1.29 101.84 1.00 106.24 0.66
GB -10085.14 126.71 -5065.69 104.21 -5288.36 82.08
GBSOL -9890.70 126.22 -4963.84 103.60 -5182.13 81.90
GBELE -35718.67 53.08 -17889.06 37.89 -17869.15 34.71
GBTOT -24688.29 84.77 -12324.73 57.75 -12281.44 58.15
# DELTA
# -----------------------
# MEAN STD
# =======================
ELE -229.38 33.97
VDW -108.02 8.36
INT 0.01 0.02
GAS -337.39 34.98
PBSUR -13.65 0.60
PBCAL 342.60 53.95
PBSOL 328.96 53.75
PBELE 113.22 47.31
PBTOT -8.43 47.38
GBSUR -13.65 0.60
GB 268.91 27.27
GBSOL 255.27 26.94
GBELE 39.53 10.22
GBTOT -82.12 10.58
Complex 2
# COMPLEX RECEPTOR LIGAND
# ----------------------- ----------------------- -----------------------
# MEAN STD MEAN STD MEAN STD
# ======================= ======================= =======================
ELE -25043.01 105.56 -12553.76 79.46 -12167.35 94.85
VDW -3983.62 45.74 -1944.52 31.38 -1937.98 30.14
INT 14716.68 73.56 7391.26 59.32 7325.41 57.01
GAS -14309.95 118.36 -7107.03 91.27 -6779.93 115.16
PBSUR 196.83 2.17 102.93 0.91 105.25 1.38
PBCAL -10582.34 100.74 -5214.25 81.66 -5724.19 80.25
PBSOL -10385.50 100.10 -5111.32 81.35 -5618.94 80.06
PBELE -35625.34 59.89 -17768.01 54.12 -17891.54 40.59
PBTOT -24695.46 77.24 -12218.35 74.61 -12398.87 62.83
GBSUR 196.83 2.17 102.93 0.91 105.25 1.38
GB -10757.18 90.59 -5292.20 63.72 -5828.65 79.10
GBSOL -10560.34 90.11 -5189.27 63.38 -5723.40 79.04
GBELE -35800.19 44.20 -17845.96 32.76 -17996.00 32.61
GBTOT -24870.30 73.82 -12296.30 60.52 -12503.32 61.84
# DELTA
# -----------------------
# MEAN STD
# =======================
ELE -321.90 42.76
VDW -101.12 8.14
INT 0.01 0.01
GAS -423.00 39.25
PBSUR -11.34 0.50
PBCAL 356.10 63.34
PBSOL 344.76 63.43
PBELE 34.21 53.60
PBTOT -78.24 53.42
GBSUR -11.34 0.50
GB 363.67 33.48
GBSOL 352.33 33.51
GBELE 41.77 12.42
GBTOT -70.68 8.68
Complex 3
# COMPLEX RECEPTOR LIGAND
# ----------------------- ----------------------- -----------------------
# MEAN STD MEAN STD MEAN STD
# ======================= ======================= =======================
ELE -25140.73 139.54 -12377.13 103.84 -12394.07 128.29
VDW -3982.08 44.99 -1942.57 32.26 -1936.49 35.78
INT 14691.27 86.41 7354.19 65.89 7337.07 61.43
GAS -14431.54 153.14 -6965.51 112.95 -6993.49 131.78
PBSUR 193.79 1.43 102.85 1.12 102.73 0.88
PBCAL -10631.17 114.15 -5513.74 87.69 -5546.47 105.89
PBSOL -10437.38 113.44 -5410.89 87.19 -5443.74 105.46
PBELE -35771.91 52.81 -17890.86 37.40 -17940.54 39.94
PBTOT -24868.92 88.79 -12376.40 69.48 -12437.23 64.90
GBSUR 193.79 1.43 102.85 1.12 102.73 0.88
GB -10884.28 109.79 -5631.87 84.98 -5657.85 104.84
GBSOL -10690.49 109.24 -5529.03 84.58 -5555.13 104.42
GBELE -36025.01 49.69 -18009.00 33.73 -18051.92 36.97
GBTOT -25122.03 89.14 -12494.54 66.05 -12548.62 61.97
# DELTA
# -----------------------
# MEAN STD
# =======================
ELE -369.54 38.67
VDW -103.01 6.13
INT 0.01 0.01
GAS -472.54 37.87
PBSUR -11.78 0.47
PBCAL 429.04 40.89
PBSOL 417.26 40.75
PBELE 59.49 18.74
PBTOT -55.28 16.69
GBSUR -11.78 0.47
GB 405.45 34.43
GBSOL 393.67 34.35
GBELE 35.90 8.75
GBTOT -78.87 6.83
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber.scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
Received on Sun May 27 2007 - 06:07:56 PDT
