Excuse me for butting into this thread and for top posting.
If this is an ordinary nucleoside triphosphate ligand, the charge
should be -4, not -3 (assuming that you are using protonation states
appropriate for pH 7). The alpha and beta phosphates each have a -1
formal charge, but the gamma is -2. Of course if it is complexed
with, e.g., magnesium, the situation is altogether more complicated.
This may or may not have something to do with your problem, but I
thought it should be mentioned.
Bud Dodson
On Sat, Jun 07, 2008 at 08:36:21AM -0400, Adrian Roitberg wrote:
> Sasha,
> One more suggestion, truly important.
>
> If you are using either Andersen or Langevin thermostats, CHANGE the
> random seed for each of your short runs.
>
> Basically, all you mdins must be modified to have a different ig value.
> Cheers
> a.
>
>
> Sasha Buzko wrote:
> >Thanks, Ross.
> >Will try it on Monday.
> >
> >Cheers
> >
> >Sasha
> >
> >
> >Ross Walker wrote:
> >>
> >>Hi Sasha,
> >>
> >>
> >>
> >>Okay, that is just weird... I suspect there is a parameter that is
> >>making something collapse onto another atom, perhaps a dodgy VDW
> >>radii. I assume all the test cases pass without problems.
> >>
> >>
> >>
> >>Something to try.
> >>
> >>
> >>
> >>Set Maxcyc=200, ncyc=200, ntpr=1 and ntwr=-1
> >>
> >>
> >>
> >>This way you will be able to see every step in the mdout file. You
> >>will also get a restart file for every step. In this way you can look
> >>at the structure immediately before it turns to NaNs and see how it
> >>differs from th initial structure. This will hopefully identify which
> >>atom / region is causing the problems.
> >>
> >>
> >>
> >>All the best
> >>
> >>Ross
> >>
> >>
> >>
> >>*From:* owner-amber.scripps.edu [mailto:owner-amber.scripps.edu] *On
> >>Behalf Of *Sasha Buzko
> >>*Sent:* Friday, June 06, 2008 4:40 PM
> >>*To:* amber.scripps.edu
> >>*Subject:* RE: AMBER: Problems simulating a protein-ligand complex
> >>
> >>
> >>
> >>Ross,
> >>The output is below. Thanks
> >>
> >>
> >> -------------------------------------------------------
> >> Amber 9 SANDER 2006
> >> -------------------------------------------------------
> >>
> >>| PMEMD implementation of SANDER, Release 9
> >>
> >>| Run on 06/06/2008 at 16:09:26
> >>
> >> [-O]verwriting output
> >>
> >>File Assignments:
> >>| MDIN:
> >>min.in
> >>| MDOUT:
> >>complex_min.out |
> >>INPCRD:
> >>complex.inpcrd
> >>| PARM:
> >>complex.prmtop |
> >>RESTRT:
> >>complex_min.rst
> >>| REFC:
> >>refc
> >>| MDVEL:
> >>mdvel
> >>| MDEN:
> >>mden
> >>| MDCRD:
> >>mdcrd |
> >>MDINFO:
> >>mdinfo
> >>|LOGFILE:
> >>logfile
> >>
> >>Here is the input file:
> >>
> >>Initial minimisation of our
> >>complex
> >>&cntrl
> >>
> >> imin=1, maxcyc=1000,
> >>ncyc=400, cut=20,
> >>ntb=0, igb=1,
> >>/
> >>
> >>
> >>
> >>
> >>| Conditional Compilation Defines Used:
> >>| DIRFRC_COMTRANS
> >>| DIRFRC_EFS
> >>| DIRFRC_NOVEC
> >>| MPI
> >>| SLOW_NONBLOCKING_MPI
> >>| PUBFFT
> >>| FFTLOADBAL_2PROC
> >>| MKL
> >>
> >>| New format PARM file being parsed.
> >>| Version = 1.000 Date = 06/06/08 Time = 16:01:47
> >>| Duplicated 0 dihedrals
> >>
> >>| Duplicated 0 dihedrals
> >>
> >>--------------------------------------------------------------------------------
> >>
> >> 1. RESOURCE USE:
> >>--------------------------------------------------------------------------------
> >>
> >>
> >>NATOM = 2694 NTYPES = 17 NBONH = 1329 MBONA = 1388
> >>NTHETH = 3017 MTHETA = 1881 NPHIH = 5748 MPHIA = 4591
> >>NHPARM = 0 NPARM = 0 NNB = 14815 NRES = 168
> >>NBONA = 1388 NTHETA = 1881 NPHIA = 4591 NUMBND = 59
> >>NUMANG = 119 NPTRA = 52 NATYP = 43 NPHB = 0
> >>IFBOX = 0 NMXRS = 46 IFCAP = 0 NEXTRA = 0
> >>NCOPY = 0
> >>
> >>Implicit solvent radii are modified Bondi radii
> >>(mbondi)
> >>--------------------------------------------------------------------------------
> >>
> >> 2. CONTROL DATA FOR THE RUN
> >>--------------------------------------------------------------------------------
> >>
> >>
> >>
> >>
> >>
> >>General flags:
> >> imin = 1, nmropt = 0
> >>
> >>Nature and format of input:
> >> ntx = 1, irest = 0, ntrx = 1
> >>
> >>Nature and format of output:
> >> ntxo = 1, ntpr = 50, ntrx = 1, ntwr
> >>= 500
> >> iwrap = 0, ntwx = 0, ntwv = 0, ntwe
> >>= 0
> >> ioutfm = 0, ntwprt = 0, idecomp = 0,
> >>rbornstat= 0
> >>
> >>Potential function:
> >> ntf = 1, ntb = 0, igb = 1, nsnb
> >>= 25
> >> ipol = 0, gbsa = 0, iesp = 0
> >> dielc = 1.00000, cut = 20.00000, intdiel = 1.00000
> >> saltcon = 0.00000, offset = 0.09000, gbalpha= 1.00000
> >> gbbeta = 0.00000, gbgamma = 0.00000, surften = 0.00500
> >> rdt = 0.00000, rgbmax = 25.00000
> >> alpb = 0
> >> scnb = 2.00000, scee = 1.20000
> >>
> >>Frozen or restrained atoms:
> >> ibelly = 0, ntr = 0
> >>
> >>Energy minimization:
> >> maxcyc = 1000, ncyc = 400, ntmin = 1
> >> dx0 = 0.01000, drms = 0.00010
> >>
> >>--------------------------------------------------------------------------------
> >>
> >> 3. ATOMIC COORDINATES AND VELOCITIES
> >>--------------------------------------------------------------------------------
> >>
> >>
> >>
> >>
> >>begin time read from input coords = 0.000 ps
> >>
> >>Number of triangulated 3-point waters found: 0
> >>| Dynamic Memory, Types Used:
> >>| Reals 81794
> >>| Integers 252050
> >>
> >>| Running AMBER/MPI version on 2 nodes
> >>
> >>
> >>--------------------------------------------------------------------------------
> >>
> >> 4. RESULTS
> >>--------------------------------------------------------------------------------
> >>
> >>
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 1 -6.8120E+03 1.3612E+01 2.1864E+02 H42 2691
> >>
> >>BOND = 361.7247 ANGLE = 397.1223 DIHED =
> >>1628.3352
> >>VDWAALS = -1261.3284 EEL = -11082.6784 EGB =
> >>-2549.3611
> >>1-4 VDW = 700.0442 1-4 EEL = 4994.1524 RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 50 -7.7370E+03 8.4612E-01 1.9291E+01 PB 2656
> >>
> >>BOND = 86.0923 ANGLE = 347.5428 DIHED =
> >>1607.9732
> >>VDWAALS = -1480.4067 EEL = -11036.0858 EGB =
> >>-2588.3621
> >>1-4 VDW = 595.7157 1-4 EEL = 4730.5444 RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 100 -7.8256E+03 6.4938E-01 1.8211E+01 CG 1860
> >>
> >>BOND = 95.2522 ANGLE = 376.9760 DIHED =
> >>1605.2109
> >>VDWAALS = -1506.3884 EEL = -11062.2867 EGB =
> >>-2567.6875
> >>1-4 VDW = 572.7459 1-4 EEL = 4660.5666 RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 150 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 200 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 250 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 300 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 350 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 400 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >> .... RESTARTED DUE TO LINMIN FAILURE ...
> >>
> >> .... RESTARTED DUE TO LINMIN FAILURE ...
> >>
> >> .... RESTARTED DUE TO LINMIN FAILURE ...
> >>
> >> .... RESTARTED DUE TO LINMIN FAILURE ...
> >>
> >> .... RESTARTED DUE TO LINMIN FAILURE ...
> >>
> >>
> >> FINAL RESULTS
> >>
> >>
> >>
> >> NSTEP ENERGY RMS GMAX NAME NUMBER
> >> 421 NaN NaN 0.0000E+00 N 1
> >>
> >>BOND = NaN ANGLE = NaN DIHED =
> >>0.0000
> >>VDWAALS = NaN EEL = NaN EGB
> >>= NaN
> >>1-4 VDW = NaN 1-4 EEL = NaN RESTRAINT =
> >>0.0000
> >>
> >> ***** REPEATED LINMIN FAILURE *****
> >>--------------------------------------------------------------------------------
> >>
> >> 5. TIMINGS
> >>--------------------------------------------------------------------------------
> >>
> >>
> >>| NonSetup CPU Time in Major Routines, Average for All Tasks:
> >>|
> >>| Routine Sec %
> >>| ------------------------------
> >>| DataDistrib 0.68 0.14
> >>| Nonbond 493.96 99.54
> >>| Bond 0.02 0.00
> >>| Angle 0.17 0.03
> >>| Dihedral 1.39 0.28
> >>| Shake 0.00 0.00
> >>| Other 0.04 0.01
> >>| ------------------------------
> >>| Total 496.26
> >>
> >>| Generalized Born CPU Time, Average for All Tasks:
> >>|
> >>| Routine Sec %
> >>| ------------------------------------
> >>| Radii Calc 37.90 7.64
> >>| Diagonal Calc 263.50 53.10
> >>| Off Diagonal Calc 192.32 38.75
> >>| Radii Distrib 0.24 0.05
> >>| ---------------------------------
> >>| Total 493.96 99.54
> >>
> >>| Master Setup CPU time: 0.03 seconds
> >>| Master NonSetup CPU time: 496.69 seconds
> >>| Master Total CPU time: 496.72 seconds 0.14 hours
> >>
> >>| Master Setup wall time: 0 seconds
> >>| Master NonSetup wall time: 261 seconds
> >>| Master Total wall time: 261 seconds 0.07 hours
> >>
> >>
> >>On Fri, 2008-06-06 at 16:34 -0700, Ross Walker wrote:
> >>
> >>Hi Sasha,
> >>
> >>
> >>
> >>Can you post the output file from the minimization? You probably have
> >>two atoms sitting on top of each other or very close.
> >>
> >>
> >>
> >>All the best
> >>
> >>Ross
> >>
> >>
> >>
> >> *From:*owner-amber.scripps.edu [mailto:owner-amber.scripps.edu]
> >> *On Behalf Of *Sasha Buzko
> >> *Sent:* Friday, June 06, 2008 4:13 PM
> >> *To:* amber.scripps.edu
> >> *Subject:* RE: AMBER: Problems simulating a protein-ligand complex
> >>
> >>
> >> Hi Ross,
> >> thank you for the detailed instructions (although I'm trying to
> >> use GB and avoid having to add explicit solvent).
> >>
> >> I did get a complex with the correct position of the ligand (used
> >> Sirius to check the prmtop/inpcrd). But at the stage of
> >> minimization I run into NaN values for all energies after about
> >> 100 steps (in the minimization out file). Not sure whether it's
> >> missing parameters or something else.. frcmod file had the following:
> >>
> >> IMPROPER
> >> c3-cc-na-cc 1.1 180.0 2.0 Using
> >> default value
> >> h5-na-cc-nd 1.1 180.0 2.0 Using
> >> default value
> >> c -cc-cd-nd 1.1 180.0 2.0 Using
> >> default value
> >> cd-nc-c -o 10.5 180.0 2.0
> >>General improper torsional angle (2 general atom types)
> >> na-nc-cd-nh 1.1 180.0 2.0 Using
> >> default value
> >> cd-hn-nh-hn 1.1 180.0 2.0 Using
> >> default value
> >> cc-cd-na-hn 1.1 180.0 2.0
> >>General improper torsional angle (2 general atom types)
> >> cd-na-cc-na 1.1 180.0 2.0 Using
> >> default value
> >>
> >>
> >> But again, I'm not sure what could cause the issue with NaN
> >> values. Since the ligand is a triphosphate, I set its charge to -3
> >> (using -nc -3 flag for antechamber). In any event, I'm a bit low
> >> on possible causes..
> >> Can you think of anything in this regard?
> >>
> >> Thanks again
> >>
> >> Sasha
> >>
> >>
> >> On Fri, 2008-06-06 at 15:55 -0700, Ross Walker wrote:
> >>
> >>
> >>
> >> Hi Sasha,
> >>
> >>
> >> I would do something along the lines of the following:
> >>
> >>
> >> 1) open protein pdb in a text editor and remove the END (at the
> >>end) and just make sure there is a ter card there. Also remove any
> >>connectivity data.
> >>
> >>
> >> 2) open the ligand pdb file and remove anything prior to the first
> >>atom definition. Go to the end and remove everything past the last
> >>atom definition and just add an END card.
> >>
> >>
> >> 3) cp protein pdb to complex.pdb
> >>
> >> Cat ligand pdb >> complex.pdb
> >>
> >>
> >> 4) load leap
> >>
> >> Source leaprc.ff99SB
> >>
> >> Source leaprc.gaff
> >>
> >> Loadamberprep ligand.prep
> >>
> >> Loadamberparams ligand.frcmod
> >>
> >> Foo = loadpdb complex.pdb
> >>
> >> Solvateoct foo TIP3PBOX 10.0
> >>
> >> Saveamberparm foo prmtop inpcrd
> >>
> >>
> >> I hope that makes sense and is what you actually want to do I.e
> >>make a prmtop and inpcrd for the solvated complex.
> >>
> >>
> >> All the best
> >>
> >> Ross
> >>
> >>
> >>
> >>
> >> From: owner-amber.scripps.edu <mailto:owner-amber.scripps.edu>
> >>[mailto:owner-amber.scripps.edu <mailto:owner-amber.scripps.edu>] On
> >>Behalf Of Sasha Buzko
> >>
> >> Sent: Friday, June 06, 2008 3:16 PM
> >>
> >> To: amber.scripps.edu <mailto:amber.scripps.edu>
> >>
> >> Subject: Re: AMBER: Problems simulating a protein-ligand complex
> >>
> >>
> >> Thank you, David.
> >>
> >>
> >> With hydrogens added in another application, the antechamber part
> >>worked.
> >>
> >> But another issue appears when I combine the protein structure
> >>with the antechamber output in xleap. The ligand is loaded as a prepin
> >>file, followed by its frcmod with missing parameters. Then I load the
> >>pdb file of the protein and use complex = combine { protein GNP },
> >>where GNP is the name of the residue assigned to the ligand. However,
> >>the ligand ends up being shifted in space far from the protein, even
> >>though the initial coordinates corresponded to the complex.. I assume
> >>that it's the result of the intermediate operations.. but is there a
> >>way to combine the two entities into the original complex?
> >>
> >>
> >> Thanks for any advice
> >>
> >>
> >> Sasha
> >>
> >>
> >>
> >>
> >>
> >> On Fri, 2008-06-06 at 11:59 -0700, David A. Case wrote:
> >>
> >> On Fri, Jun 06, 2008, Sasha Buzko wrote:
> >>
> >> >
> >> > The structure has correct connectivity and came directly from a PDB
> >>
> >> > file. Since the ligand PDB file is not that large, I'm pasting
> >>it below.
> >>
> >> > Thank you for any suggestions.
> >>
> >>
> >> You don't have any hydrogen atoms in your input structure.
> >>Antechamber
> >>
> >> doesn't know how to add hydrogens...you need to draw them in by
> >>hand, or
> >>
> >> use some other model building program to add all of the hydrogens.
> >>
> >>
> >> ...hope this helps...dac
> >>
> >>
> >>
> >>-----------------------------------------------------------------------
> >>
> >> The AMBER Mail Reflector
> >>
> >> To post, send mail to amber.scripps.edu <mailto:amber.scripps.edu>
> >>
> >> To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
> >>
> >> to majordomo.scripps.edu <mailto:majordomo.scripps.edu>
> >>
> >>
> >>
> >>-----------------------------------------------------------------------
> >>
> >> The AMBER Mail Reflector
> >>
> >> To post, send mail to amber.scripps.edu <mailto:amber.scripps.edu>
> >>
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> >>
> >> to majordomo.scripps.edu <mailto:majordomo.scripps.edu>
> >>
> >
>
> --
> Dr. Adrian E. Roitberg
> Associate Professor
> Quantum Theory Project
> Department of Chemistry
>
> Senior Editor. Journal of Physical Chemistry
> American Chemical Society
>
> University of Florida PHONE 352 392-6972
> P.O. Box 118435 FAX 352 392-8722
> Gainesville, FL 32611-8435 Email adrian.qtp.ufl.edu
> -----------------------------------------------------------------------
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> To unsubscribe, send "unsubscribe amber" (in the *body* of the email)
> to majordomo.scripps.edu
--
M. L. Dodson
Business Email: activesitedynamics-at-comcast-dot-net
Personal Email: mldodson-at-comcast-dot-net
Phone: eight_three_two-56_three-386_one
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Received on Sun Jun 08 2008 - 06:08:18 PDT
