[gmx-users] DNA-Protein complex MD failing

[Justin Lemkul]

On 2/20/15 7:21 AM, virginia miguel wrote:
> Hi, Thanks for your reply, I am using  AMBER99SB-ILDN protein, nucleic AMBER94...about the settings, of that I am not certain since I took the parameters for a couple of papers and an example .mdp I found googling but not with the exact Amber force field. Then I modified it to use gpu so rvdw=rcoulomb. And thats my major concern, which are the correct values for these settings!.
>

Start with what's specified in dx.doi.org/10.1002/prot.22711

Beyond that, simplify the system.  Make sure the protein alone runs stably, the 
DNA alone, etc.  It could be that your starting configuration is simply not 
stable.  The general guidelines are in

http://www.gromacs.org/Documentation/Terminology/Blowing_Up

-Justin

>
> Dra. Virginia MiguelInstituto de Investigaciones Biológicasy Tecnológicas (IIBYT)
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> I arise in the morning torn between a desire to improve the world and a
> desire to enjoy the world. This makes it hard to plan the day. (E.B. White)
>
>
> On 2/19/15 12:55 PM, virginia miguel wrote:
>> Hi everyone; I am tryingto run a simulation of a DNA-protein complex obtained by docking of a dsDNA of18bp to a crystal structure of the recA protein using GPU. I used amber ff, adodecahedron cell with 15A of distance from the surface of the complex and neutralizedwith counter ions (42 NA+, since my system charge is -42). I minimized with steepest descendent for 4000 steps and the obtainedenergies are ok, this is my minimization mdp
>>
>> define      = -DFLEXIBLE
>> constraints = none
>> integrator  = steep
>> dt          = 0.001 ; ps !
>> nsteps      = 10000
>> nstlist    = 10
>> ns_type    = grid
>> rlist      = 1.0
>> coulombtype = PME
>> rcoulomb    = 1.0
>> vdwtype    = cut-off
>> rvdw        = 1.0
>> fourierspacing = 0.08
>> fourier_nx    = 0
>> fourier_ny    = 0
>> fourier_nz    = 0
>> pme_order      = 8
>> ewald_rtol    = 1e-5
>> optimize_fft  = yes
>> ;
>> ; Energy minimizing stuff
>> ;
>> emtol          = 1000.0
>> emstep        = 0.01
>>
>>    But when Iintend to run de md protocol a segmentation error occurs and the dynamicsbreaks. I have tried to start with NVT and NPT ensembles, with positionrestrictions of all, the backbone and no restrictions at all. Also with temperaturesas low as 100K but it the dynamics keep on blowing up. I have these warnings
>>
>> "Step 663, time 0.663 (ps)  LINCS WARNING
>> relative constraint deviation after LINCS:
>> rms 329.431423, max 141697.812500 (between atoms 17283 and 17284)
>> bonds that rotated more than 30 degrees"
>> ---and finally--
>> "
>> WARNING: Listed nonbonded interaction between particles 12971 and 12990
>> at distance 2.320 which is larger than the table limit 2.200 nm.
>>
>> This is likely either a 1,4 interaction, or a listed interaction inside
>> a smaller molecule you are decoupling during a free energy calculation.
>> Since interactions at distances beyond the table cannot be computed,
>> they are skipped until they are inside the table limit again. You will
>> only see this message once, even if it occurs for several interactions.
>>
>> IMPORTANT: This should not happen in a stable simulation, so there is
>> probably something wrong with your system. Only change the table-extension
>> distance in the mdp file if you are really sure that is the reason.
>>
>>
>> ./rungromacs: line 10:  8006 Segmentation fault "
>>
>>
>> I do notknow what the correct settings of .mpd ?I am using the following that resultsfroma a review I did of several works working with DNA and amber in gromacs. This is my md .mdp
>>    title = AMBER
>> define = -DFLEXIBLE
>
> Don't run dynamics with flexible water.
>
>> cpp = /usr/bin/cpp -traditional
>>
>> ; RUN CONTROL PARAMETERS
>>                      integrator = md
>> ; Start time and timestep in ps
>>                          tinit = 0
>>                              dt = 0.002
>>                        nsteps  = 100000
>>
>> ; mode for center of mass motion removal
>>                      comm-mode  = Linear
>> ; number of steps for center of mass motion removal
>>                        nstcomm  = 1
>> ; group(s) for center of mass motion removal
>>                      comm_grps  = system
>>
>>
>> ; OUTPUT CONTROL OPTIONS
>> ; Output frequency for coords (x), velocities (v) and forces (f)
>> nstxout                  = 5000
>> nstvout                  = 5000
>> nstfout                  = 5000
>>
>> ; Checkpointing helps you continue after crashes
>> nstcheckpoint            = 1000
>>
>> ; Output frequency for energies to log file and energy file
>> nstlog                  = 5000
>> nstenergy                = 5000
>>
>> ; Output frequency and precision for xtc file
>> nstxtcout                = 5000
>> xtc-precision            = 1000
>>
>> ; This selects the subset of atoms for the xtc file. You can
>> ; select multiple groups. By default all atoms will be written.
>> xtc_grps                = !SOL
>>
>> ; Selection of energy groups
>> energygrps              = !SOL SOL
>>
>> ; NEIGHBOR SEARCHING
>>                    nstlist = 10
>>                    ns_type = grid
>>                        pbc = xyz
>> ; nblist cut-off
>>                      rlist  = 1.2
>>
>> ; domain-decomposition    = no
>>
>>
>> ; ELECTROSTATICS
>>                      rcoulomb = 1.0
>>                  coulombtype = PME
>> ; EWALD
>> fourierspacing            = 0.10
>> pme_order                  = 6
>> ewald_rtol                = 1e-5
>> optimize_fft              = yes
>>
>>
>> ; VDW
>> vdwtype                    = switch
>> rvdw_switch                = 0.8
>> rvdw                      = 1.0
>>
>
> Are these nonbonded settings right?  They seem a bit random.  Which of the AMBER
> force fields are you using?
>
> -Justin
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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