[gmx-users] Fwd: FEP calculations problem and posible BUG on GROMACS-3.3.2

Daniel Adriano Silva M dadriano at gmail.com
Mon Oct 15 22:16:26 CEST 2007


Hello,

I have three problems here. First, I'm trying to made FEP calculations
in order to calculate the DG of binding for a small ligand (aminoacid)
to a protein, but my ligand (arginine) have a net charge of +1e, so
when I "disappear" this ligand the system takes a total charge of -1e
and I get the corresponding "note":

*  State B has non-zero total charge: -1.000001e+00

My question is: what can I do?, because if at same time I try to
appear a Na+ atom I will be calculating the DG of binding of my ligand
plus the solvatation energy of one Na+ atom. In the other case, if I
doesn't compensate the charge I think PME will not work correctly.

A second problem is that I'm getting this:
WARNING 1 [file "topol_S.itp", line 39]:
 Some parameters for bonded interaction involving perturbed atoms are
 specified explicitly in state A, but not B - copying A to B

so I inferred that the problem is that I need also to specify a
B-state for bonds so for example I taked the line:
*;  ai    aj funct            c0            c1            c2            c3
*    1     2     2    gb_2
and I transformed this to:
*;  ai    aj funct            c0            c1            c2            c3
*    1     2     2         gb_2         gb_2

I made this for bonds, angles and dihedrals. My question is:  is
correct my method?, and what is the meaning of this B-states?, it's to
say in what case I will want different bonds, angles, etc.. on my
simulation, and what happens If I doesn't specify this, will GROMACS
made the duplication of A state automatically?
Also I think it's important to mention that I have the topology of the
ligand: topol_S.itp, and the corresponding to the protein:
topol_E.itp. But I only get the warning  for topol_S (disapearing
ligand), but not for the protein where that parameters on B-state are
not explicitly annotated. Question: why?

The third problem is what I think can be a BUG on 3.3.2. This warning
doesn't appear on 3.3.1:

*WARNING 2 [file aminoacids.dat, line 1]:
*  T-Coupling group protein has fewer than 10% of the atoms (2381 out of
*  36249)
*  Maybe you want to try Protein and Non-Protein instead?

I strongly think this is an error because in my MDP file I have explicitly:
* tc-grps         = protein non-protein

and because in the GROMPP out also appears:
* T-Coupling       has 2 element(s): Protein Non-Protein

I paste the output of grompp and my mdp:

GROMPP
#################################################################
creating statusfile for 12 nodes...
calling /usr/bin/cpp...
processing topology...
turning all bonds into constraints...
turning all bonds into constraints...
turning all bonds into constraints...
turning all bonds into constraints...
turning all bonds into constraints...
#  G96ANGLES:   3528
#      PDIHS:   1269
#      IDIHS:   1158
#       LJ14:   3898
#     CONSTR:   2413
#     SETTLE:   11289
Analysing residue names:
There are: 11290      OTHER residues
There are:   239    PROTEIN residues
There are:     0        DNA residues
Analysing Protein...
Analysing Other...
e frame at or first after this time.
-np          int    12      Generate statusfile for # nodes
-[no]shuffle bool   no      Shuffle molecules over nodes
-[no]sort    bool   no      Sort molecules according to X coordinate
-[no]rmvsbds bool   yes     Remove constant bonded interactions with virtual
                           sites
-load        string         Releative load capacity of each node on a
                           parallel machine. Be sure to use quotes around
                           the string, which should contain a number for
                           each node
-maxwarn     int    10      Number of warnings after which input processing
                           stops
-[no]check14 bool   no      Remove 1-4 interactions without Van der Waals
-[no]zero    bool   no      Set parameters for bonded interactions without
                           defaults to zero instead of generating an error
-[no]renum   bool   yes     Renumber atomtypes and minimize number of
                           atomtypes


Back Off! I just backed up LAMBDA_0.0/mdout_lambda_0.0.mdp to
LAMBDA_0.0/#mdout_lambda_0.0.mdp.19#
checking input for internal consistency...
Generated 165 of the 1596 non-bonded parameter combinations
Excluding 3 bonded neighbours for Protein_E 1
Excluding 3 bonded neighbours for Protein_S 1
Excluding 2 bonded neighbours for SOL 11289
Excluding 1 bonded neighbours for NA+ 1
Excluding 1 bonded neighbours for CL- 0
NOTE:
 State B has non-zero total charge: -1.000001e+00

processing coordinates...
double-checking input for internal consistency...
Velocities were taken from a Maxwell distribution at 310 K
renumbering atomtypes...
converting bonded parameters...
Walking down the molecule graph to make shake-blocks
initialising group options...
processing index file...
Opening library file
/global/home/est/dasm/PROGRAMAS/bin/../gromacs-3.3.2/build/share/gromacs/top/aminoacids.dat
WARNING 1 [file aminoacids.dat, line 1]:
 T-Coupling group protein has fewer than 10% of the atoms (2381 out of
 36249)
 Maybe you want to try Protein and Non-Protein instead?
Making dummy/rest group for Acceleration containing 36249 elements
Making dummy/rest group for Freeze containing 36249 elements
Making dummy/rest group for VCM containing 36249 elements
Number of degrees of freedom in T-Coupling group Protein is 4729.80
Number of degrees of freedom in T-Coupling group Non-Protein is 67734.20
Making dummy/rest group for User1 containing 36249 elements
Making dummy/rest group for User2 containing 36249 elements
Making dummy/rest group for XTC containing 36249 elements
Making dummy/rest group for Or. Res. Fit containing 36249 elements
Making dummy/rest group for QMMM containing 36249 elements
T-Coupling       has 2 element(s): Protein Non-Protein
Energy Mon.      has 2 element(s): Protein Non-Protein
Acceleration     has 1 element(s): rest
Freeze           has 1 element(s): rest
User1            has 1 element(s): rest
User2            has 1 element(s): rest
VCM              has 1 element(s): rest
XTC              has 1 element(s): rest
Or. Res. Fit     has 1 element(s): rest
QMMM             has 1 element(s): rest
Checking consistency between energy and charge groups...
Calculating fourier grid dimensions for X Y Z
Using a fourier grid of 72x72x70, spacing 0.114 0.114 0.117
splitting topology...
Walking down the molecule graph to make shake-blocks
There are 12315 charge group borders and 11292 shake borders
There are 11292 total borders
Division over nodes in atoms:
   3020    3021    3021    3021    3021    3021    3021    3021
3021    3021    3021    3019
writing run input file...

Back Off! I just backed up LAMBDA_0.0/lambda_0.0.tpr to
LAMBDA_0.0/#lambda_0.0.tpr.19#

There was 1 warning
#################################################################
#################################################################

MDP
#################################################################
title                =  dsilva Pos-Res
cpp                  =  /usr/bin/cpp

integrator      = md
dt               = 0.002
nsteps          = 1500000

pbc             = xyz

nstlist         = 10
rlist           = 1.0
ns_type         = grid

coulombtype     = pme
rcoulomb        = 1.0

vdwtype         = cut-off
rvdw            = 1.0

tcoupl          = Berendsen
tc-grps         = protein non-protein
tau-t           = 0.1 0.1
ref-t           = 310 310
Pcoupl          = Berendsen
pcoupltype      = isotropic
tau-p           = 1.0
ref-p           = 1.0
compressibility = 4.5e-5

fourierspacing       =  0.12
pme_order            =  4
optimize_fft         =  yes
ewald_rtol           =  1e-5
gen_vel              =  yes
gen_temp             =  310
gen_seed             =  173529
constraints          =  all-bonds
constraint_algorithm =  lincs
lincs_order          =  4

; Free energy control stuff
free_energy              = yes
init_lambda              = 0.0
delta-lambda             = 0
sc_alpha                 = 0.5
sc_sigma                 = 0.3
sc_power                 = 1.0

DispCorr                 = EnerPres

nstxout             =  1000
nstvout             =  1000
nstfout             =  0
nstlog              =  40
nstenergy           =  40
energygrps          =  Protein non-protein
#################################################################

Any observation and/or recommendation will be welcome.

Thanks in advance.
Daniel Silva



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