I ran a short minimization (1000 steps) restraining only heavy atoms of protein and ligand and letting free water and ions.
I used the XMIN method.
Checking the last min. steps, the ligand (6amino purine) looks flat.Energy and RMS are the following:
NSTEP ENERGY RMS GMAX NAME NUMBER
0 -4.3341E+04 8.0097E+02 8.6466E+04 HB3 2407
BOND = 225.1387 ANGLE = 974.3270 DIHED = 2406.0812
VDWAALS = 30751.5018 EEL = -93128.1761 HBOND = 0.0000
1-4 VDW = 6178.8768 1-4 EEL = 9251.4088 RESTRAINT = 0.0000
NSTEP ENERGY RMS GMAX NAME NUMBER
1000 -1.0304E+05 4.2733E+00 7.0121E+02 C4 3843
BOND = 7022.7201 ANGLE = 539.6263 DIHED = 2333.6829
VDWAALS = 14795.8479 EEL = -137617.8581 HBOND = 0.0000
1-4 VDW = 822.9231 1-4 EEL = 8925.1673 RESTRAINT = 133.2156
EAMBER = -103177.8905
The final structure was used to run a short MD (15ps) to relax the solvent.
Complex's heavy atoms were restrained as before.
After 4 steps Sander stopped with the following message:
vlimit exceeded for step 4; vmax = 150.3337
Coordinate resetting (SHAKE) cannot be accomplished,
deviation is too large
NITER, NIT, LL, I and J are : 0 3 1927 3834 3844
Note: This is usually a symptom of some deeper
problem with the energetics of the system.
I analyzed the 4 frames obtained. At the frame 1, the ligand molecule was completely distorted. And so now the error message makes more sense, since atoms 3834 and 3844 (N9 and H9, respectively) deviated a lot after the 1st MD step.
I am wondering that this behavior is related to the parameters I obtained for the 6 amino purine using Antechamber.
Any suggestions to solve this problem?
Vale
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Valentina Romano | PhD Student | Biozentrum, University of Basel & SIB Swiss Institute of Bioinformatics
Klingelbergstrasse 61 | CH-4056 Basel |
Phone: +41 61 267 15 80
________________________________________
From: Daniel Roe [daniel.r.roe.gmail.com]
Sent: Monday, May 12, 2014 8:00 PM
To: AMBER Mailing List
Subject: Re: [AMBER] Analysis of minimization stage
Hi,
On Mon, May 12, 2014 at 10:26 AM, Valentina Romano
<valentina.romano.unibas.ch> wrote:
> restraintmask=':1-246.CA,C,O,N | .3834-3848',
I don't think this is what you want if atom range 3834-3848 includes
hydrogen. During minimization you want all of your hydrogen atoms to
minimize as much as possible. This way during MD when you turn on
SHAKE (presumably just for bonds to H atoms), all of your X-H bond
lengths are in a good place. You really only want to restrain your
heavy atoms initially. Did you check the last few steps of your
minimization? Does it look flat? What is your RMS gradient? If your
structure is not well-minimized prior to running any MD you are
potentially setting yourself up for vlimit errors. Also, have you
tried using XMIN instead of steepest descent for minimization?
-Dan
> ntpr=1, ntwx=1, ntwr=100
>
> Atoms from 3834 to 3848 are ligand's atoms (with H atoms).
>
> I analyzed the output frames and the ligand was much more stable then before.
> (The energy was flat and no overlaps were detected).
>
> This structure was used as strating point for a short MD (to relax solvent molecules):
>
> 15ps MD PknG-Adenine complex: restraints on PknG-Ade residues while the solvent is leeting free
> to relax
> &cntrl
> imin=0,
> irest=0,
> ntx=1,
> ig=-1,
> ntb=1,
> ntr=1,
> cut=10,
> ntc=2,
> ntf=2,
> tempi=300.0,
> temp0=300.0,
> ntt=3,
> gamma_ln=5.0,
> nstlim=15000, dt=0.001,
> ntpr=1, ntwx=1, ntwr=1000
> restraint_wt = 10.0,
> restraintmask=':1-246.CA,C,O,N | .3834-3848'
> /
> Sander stopped again at the begining:
>
> vlimit exceeded for step 1; vmax = 82.0601
>
> Coordinate resetting (SHAKE) cannot be accomplished,
> deviation is too large
> NITER, NIT, LL, I and J are : 0 3 1923 3841 3848
>
> Note: This is usually a symptom of some deeper
> problem with the energetics of the system.
>
> If I restrained all ligand's atoms, why atoms 3841 and 3848 are still causing a problem?
>
> Analizing the output file i saw a message related to the charge of the whole system:
>
> Sum of charges from parm topology file = 0.00099988
> Forcing neutrality...
>
> Could it be a cause of my problem?
>
> I ran the MD as:
>
> sander -O -i PknGAde-wt-md.in -o PknGAde-wt-md.out -p ../PknGAde_params/PknGHAdeH_ion_wt.prmtop -c PknGAde-wt-min.rst -r PknGAde-wt-md.rst -ref PknGAde-wt-min.rst -x PknGAde-wt-md.mdcrd &
>
> Thus the set of initial coord and the ref coord are the same (both are the minimized structure), is it correct?
>
> Vale
>
> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
> Valentina Romano | PhD Student | Biozentrum, University of Basel & SIB Swiss Institute of Bioinformatics
> Klingelbergstrasse 61 | CH-4056 Basel |
>
> Phone: +41 61 267 15 80
>
>
> ________________________________________
> From: Jason Swails [jason.swails.gmail.com]
> Sent: Monday, May 12, 2014 4:18 PM
> To: amber.ambermd.org
> Subject: Re: [AMBER] Analysis of minimization stage
>
> On Mon, 2014-05-12 at 09:59 -0400, David A Case wrote:
>> On Mon, May 12, 2014, Valentina Romano wrote:
>> >
>> > CPPTRAJ: Trajectory Analysis. V13.22
>> > ___ ___ ___ ___
>> > | \/ | \/ | \/ |
>> > _|_/\_|_/\_|_/\_|_
>> > AmberParm Title: [default_name]
>> > Radius Set: modified Bondi radii (mbondi)
>> > INPUT: Reading Input from file PknGAde-wt-min.check_overlap
>> > [trajin PknGAde-wt-min.rst]
>> > [PknGAde-wt-min.rst] contains 1 frames.
>> > [checkoverlap]
>>
>> Try adding the "reportfile overlaps.dat" to the checkoverlap command.
>> I'm always uncertain about when cpptraj writes things to stdout, and when
>> they go to one of the data files.
>
> Whenever I've used checkoverlaps before the report gets printed to
> stdout...
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
>
>
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>
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--
-------------------------
Daniel R. Roe, PhD
Department of Medicinal Chemistry
University of Utah
30 South 2000 East, Room 201
Salt Lake City, UT 84112-5820
http://home.chpc.utah.edu/~cheatham/
(801) 587-9652
(801) 585-6208 (Fax)
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Received on Tue May 13 2014 - 08:00:02 PDT
