psfgen gets ATP chiral atoms wrong

From: John Wise (jwise_at_mail.smu.edu)
Date: Mon Jul 24 2006 - 15:43:23 CDT

Dear Listmembers,

If you use ATP residues built by psfgen and CHARMM27 All-Hydrogen
Nucleic Acid Topology Files, I believe that the resulting molecule has
mistakes in its chiral centers that may introduce artifacts in your
simulation results.

Our group does ESR measurements using various stable radical molecular
probes and one of these is a modified ATP molecule. In the process of
building and testing topology and parameter files for simulating this
new residue, I have noticed that psfgen inverts the configuration of the
C1' and C3' chiral centers when it builds an all hydrogen ATP using
crystallographic (heavy atom) coordinates of ATP. This will definitely
spoil any analysis using this ATP residue since the molecule built by
psfgen is not ATP (it does not contain ribose, but an enantiomer of ribose).

For example, using the top_all27_prot_na.inp topology file and ATP
coordinates taken from 1DX4 (see atp.pdb below), building an all
hydrogen ATP results in inverted chiral centers at C1' and C3' (or
relatively speaking C2' and C4'). The incorrect configuration is visible
right away, even though the top_all27_prot_na_inp topology file fails to
set the C4' hydrogen. It is easier to see after minimization (see the
resulting minimized "incorrect ATP" - atp_test_min.pdb below). The
problem is that the configuration at these chiral atoms is correct in
the original heavy atom pdb coordinates, but I believe psfgen sets them
wrong while it is building the all hydrogen ATP.

Viewing the correct configuration for beta-D-ribofuranosyl residues in
ATP in either C3'-endo or C2'-endo forms has the adenine and C5'
substituents on the opposite "side" of the ring to the C2'- and C3'-OH
groups. psfgen does not get this correct.

I have included the build script (atp_test.pgn) and the minimization
script (atp_test_min.conf) for anyone interested in reproducing this
(see below). Note that if you try to reproduce this with the
minimization using par_all27_prot_na_lipids_full.inp with ATP built with
top_all27_prot_na.inp you will have to change the C2' and C4' ATOM-types
for residue ATP in top_all27_prot_na.inp to CN7B and CN8B respectively
(see old posts in the list for resolution of this problem).

Variations I have tried include:
(a) Eliminating the chiral atoms from the coordinate file and relying on
the IC table to set them. Still does not result in the correct chiral
configurations.

(b) I have tried a number of coordinates for ATP from other pdb files -
same result.

(c) Using the latest top and par files (c32b1) - same result.

(d) Rewriting the IC table using an experimentally (NMR) determined all
hydrogen ATP analog structure to explicitely set the chirality at all of
the chiral centers in the IC table. (Anyone who wants these new top
files, please ask and I'll send them right out.) Although the new
topology file results in correct configurations at C1', C2' and C4' (and
the C4' hydrogen sets properly), the resultant "ATP" still does not have
the correct configuration for the C3' atom.

I am really perplexed by this and am running out of ideas to try.

It would be great if someone could prove me wrong about this!
Any help would be greatly appreciated.

Thanks in advance,
John

Files to reproduce this:

(If you use top_all27_prot_na.inp, don't forget to change the C2' and
C4' ATOM types - see above).

atp.pdb (original no hydrogen coordinates from 1DX4)

 CRYST1 177.820 68.989 56.593 90.00 104.15 90.00 P 1 1
ATOM 1 PG ATP X 676 14.097 0.957 15.066 1.00 15.67
ATOM 2 O1G ATP X 676 15.430 0.883 15.756 1.00 17.70
ATOM 3 O2G ATP X 676 12.862 0.767 15.836 1.00 15.53
ATOM 4 O3G ATP X 676 14.243 -0.076 13.974 1.00 13.95
ATOM 5 PB ATP X 676 14.852 3.282 13.423 1.00 12.74
ATOM 6 O1B ATP X 676 16.289 2.919 13.320 1.00 15.00
ATOM 7 O2B ATP X 676 14.475 3.413 12.017 1.00 15.72
ATOM 8 O3B ATP X 676 13.934 2.348 14.286 1.00 15.28
ATOM 9 PA ATP X 676 15.477 5.919 14.499 1.00 13.47
ATOM 10 O1A ATP X 676 16.312 5.772 15.724 1.00 13.31
ATOM 11 O2A ATP X 676 16.224 6.277 13.300 1.00 13.42
ATOM 12 O3A ATP X 676 14.624 4.611 14.270 1.00 11.30
ATOM 13 O5* ATP X 676 14.361 6.949 14.812 1.00 15.95
ATOM 14 C5* ATP X 676 13.331 7.464 13.937 1.00 13.15
ATOM 15 C4* ATP X 676 12.244 8.018 14.821 1.00 13.39
ATOM 16 O4* ATP X 676 12.824 9.043 15.673 1.00 15.92
ATOM 17 C3* ATP X 676 11.052 8.645 14.062 1.00 15.86
ATOM 18 O3* ATP X 676 9.792 8.347 14.700 1.00 16.75
ATOM 19 C2* ATP X 676 11.403 10.126 14.183 1.00 16.79
ATOM 20 O2* ATP X 676 10.264 10.991 14.099 1.00 16.14
ATOM 21 C1* ATP X 676 12.108 10.232 15.567 1.00 14.13
ATOM 22 N9 ATP X 676 12.937 11.424 15.757 1.00 12.81
ATOM 23 C8 ATP X 676 13.995 11.865 15.027 1.00 10.25
ATOM 24 N7 ATP X 676 14.490 13.007 15.514 1.00 15.38
ATOM 25 C5 ATP X 676 13.697 13.308 16.608 1.00 13.47
ATOM 26 C6 ATP X 676 13.689 14.373 17.556 1.00 15.40
ATOM 27 N6 ATP X 676 14.530 15.409 17.536 1.00 19.72
ATOM 28 N1 ATP X 676 12.752 14.389 18.568 1.00 14.41
ATOM 29 C2 ATP X 676 11.837 13.329 18.635 1.00 11.77
ATOM 30 N3 ATP X 676 11.766 12.299 17.803 1.00 9.60
ATOM 31 C4 ATP X 676 12.738 12.329 16.802 1.00 9.57
END

atp_test.pgn (the script I used to build atp_test.psf and atp_test.pdb)

# You need to create working directory "output" in the build directory;
    # You need to remove old output files before running again
    # from shell, run: rm -f output/*.pdb output/*.psf
    resetpsf
    package require psfgen
    # correct topology file needs to be in ../toppar
    topology ../toppar/top_all27_prot_na.inp
    # atp.pdb needs to be in ../common
    segment X {
    pdb ../common/atp.pdb
    }
    # patches should be added here
    writepsf output/atp_test.psf
    pdbalias residue HIS HSE
    pdbalias atom ILE CD1 CD
   
    coordpdb ../common/atp.pdb X
    guesscoord
    writepdb output/atp_test.pdb
    # exit

atp_test_min.conf (the conf file to minimize the ATP in vacuo)

    #############################################################
    ## JOB DESCRIPTION ##
    #############################################################
   
    # Minimization of
    # atp_test
    # in vacuo
    #
   
    #############################################################
    ## ADJUSTABLE PARAMETERS ##
    #############################################################
   
    structure ../common/atp_test.psf
    coordinates ../common/atp_test.pdb
    set outputname atp_test_min
    set temperature 310
    firsttimestep 0
   
    #############################################################
    ## SIMULATION PARAMETERS ##
    #############################################################
   
    # Input
    paraTypeCharmm on
    parameters ../toppar/par_all27_prot_na_lipids_full.inp
    temperature $temperature ;# if restarting
   
    # Force-Field Parameters
    exclude scaled1-4
    1-4scaling 1.0
    cutoff 12.
    switching on
    switchdist 10.
    pairlistdist 13.5
   
    # Integrator Parameters
    timestep 1.0 ;# 1fs/step
    # rigidBonds water ;# "all" needed for 2fs steps
    nonbondedFreq 1
    fullElectFrequency 2
    stepspercycle 10
   
    # Constant Temperature Control
    langevin on ;# do langevin dynamics
    langevinDamping 5 ;# damping coefficient (gamma) of 5/ps
    langevinTemp $temperature
    langevinHydrogen off ;# don't couple langevin bath to hydrogens
   
    # Output
    outputName $outputname
    restartfreq 500 ;# 500steps = every 1/2 ps
    dcdfreq 500 ;# 500steps = every 1/2 p
    xstFreq 250
    outputEnergies 100
    outputPressure 100
    outputTiming 1000
   
    # minimize
    minimize 3000

atp_test_min.pdb (results of the psfgen build and namd2 minimization)

CRYST1 1.000 1.000 1.000 90.00 90.00 90.00 P 1 1
ATOM 1 C4' ATP X 676 13.847 8.387 15.083 1.00 0.00 X
ATOM 2 H4' ATP X 676 14.762 8.884 14.696 1.00 0.00 X
ATOM 3 O4' ATP X 676 13.327 9.230 16.160 1.00 0.00 X
ATOM 4 C1' ATP X 676 12.351 10.102 15.638 1.00 0.00 X
ATOM 5 H1' ATP X 676 11.399 9.843 16.156 1.00 0.00 X
ATOM 6 C5 ATP X 676 12.886 13.573 16.529 1.00 0.00 X
ATOM 7 N7 ATP X 676 14.104 13.281 15.924 1.00 0.00 X
ATOM 8 C8 ATP X 676 13.975 12.023 15.572 1.00 0.00 X
ATOM 9 H8 ATP X 676 14.744 11.423 15.076 1.00 0.00 X
ATOM 10 N9 ATP X 676 12.754 11.478 15.896 1.00 0.00 X
ATOM 11 N1 ATP X 676 11.142 14.717 17.658 1.00 0.00 X
ATOM 12 C2 ATP X 676 10.441 13.585 17.551 1.00 0.00 X
ATOM 13 H2 ATP X 676 9.433 13.610 17.975 1.00 0.00 X
ATOM 14 N3 ATP X 676 10.798 12.416 17.020 1.00 0.00 X
ATOM 15 C4 ATP X 676 12.045 12.474 16.518 1.00 0.00 X
ATOM 16 C6 ATP X 676 12.394 14.740 17.148 1.00 0.00 X
ATOM 17 N6 ATP X 676 13.115 15.865 17.278 1.00 0.00 X
ATOM 18 H61 ATP X 676 12.704 16.608 17.795 1.00 0.00 X
ATOM 19 H62 ATP X 676 14.071 15.886 17.001 1.00 0.00 X
ATOM 20 C2' ATP X 676 12.213 9.833 14.151 1.00 0.00 X
ATOM 21 H2'' ATP X 676 12.822 10.542 13.546 1.00 0.00 X
ATOM 22 O2' ATP X 676 10.866 9.864 13.728 1.00 0.00 X
ATOM 23 H2' ATP X 676 10.777 9.099 13.136 1.00 0.00 X
ATOM 24 C3' ATP X 676 12.769 8.438 13.992 1.00 0.00 X
ATOM 25 H3' ATP X 676 12.028 7.629 14.197 1.00 0.00 X
ATOM 26 O3' ATP X 676 13.335 8.323 12.683 1.00 0.00 X
ATOM 27 H3T ATP X 676 13.776 7.420 12.629 1.00 0.00 X
ATOM 28 C5' ATP X 676 14.192 7.004 15.635 1.00 0.00 X
ATOM 29 H5' ATP X 676 13.305 6.332 15.526 1.00 0.00 X
ATOM 30 H5'' ATP X 676 14.403 7.068 16.723 1.00 0.00 X
ATOM 31 O5' ATP X 676 15.384 6.497 14.996 1.00 0.00 X
ATOM 32 PA ATP X 676 15.311 5.411 13.826 1.00 0.00 X
ATOM 33 O1A ATP X 676 16.703 4.909 13.752 1.00 0.00 X
ATOM 34 O2A ATP X 676 14.848 6.259 12.693 1.00 0.00 X
ATOM 35 O3A ATP X 676 14.393 4.431 14.523 1.00 0.00 X
ATOM 36 PB ATP X 676 13.445 3.809 13.391 1.00 0.00 X
ATOM 37 O1B ATP X 676 14.245 3.181 12.234 1.00 0.00 X
ATOM 38 O2B ATP X 676 12.390 4.879 13.047 1.00 0.00 X
ATOM 39 O3B ATP X 676 12.735 2.599 14.303 1.00 0.00 X
ATOM 40 PG ATP X 676 11.610 1.380 14.531 1.00 0.00 X
ATOM 41 O1G ATP X 676 12.362 0.223 15.197 1.00 0.00 X
ATOM 42 O2G ATP X 676 10.532 1.954 15.453 1.00 0.00 X
ATOM 43 O3G ATP X 676 11.054 0.988 13.162 1.00 0.00 X
END

-- 
John G. Wise, Ph.D.
Department of Biological Sciences
Southern Methodist University
Dallas, TX 75275
Office - Room 332 Dedman Life Sciences
Tel. 214 768 3426

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