[gmx-users] multiple ligands topology
Justin Lemkul
jalemkul at vt.edu
Mon Feb 16 13:42:11 CET 2015
On 2/16/15 3:49 AM, Jennifer Vo wrote:
> Dear Justin,
> Many thanks again. I just define a small box then insert molecules and let
> it floating nearby the protein, then redefine the actual box for the real
> concentration of protein.
> The maxwarn 27 is from this
> "NOTE 1 [file em_ion.mdp]:
> With Verlet lists the optimal nstlist is >= 10, with GPUs >= 20. Note
> that with the Verlet scheme, nstlist has no effect on the accuracy of
> your simulation.
> Setting the LD random seed to 2002995045
> WARNING 1 [file my_ligand_atomtypes.itp, line 3]:
> Overriding atomtype CA
>
> WARNING 2 [file my_ligand_atomtypes.itp, line 4]:
> Overriding atomtype H4
>
> WARNING 3 [file my_ligand_atomtypes.itp, line 5]:
> Overriding atomtype HA
>
> WARNING 4 [file my_ligand_atomtypes.itp, line 6]:
> Overriding atomtype C
>
> WARNING 5 [file my_ligand_atomtypes.itp, line 7]:
> Overriding atomtype O
>
> WARNING 6 [file my_ligand_atomtypes.itp, line 8]:
> Overriding atomtype N
>
> WARNING 7 [file my_ligand_atomtypes.itp, line 9]:
> Overriding atomtype H
>
> WARNING 8 [file my_ligand_atomtypes.itp, line 10]:
> Overriding atomtype N*
>
> WARNING 9 [file my_ligand_atomtypes.itp, line 11]:
> Overriding atomtype CT
>
> WARNING 10 [file my_ligand_atomtypes.itp, line 12]:
> Overriding atomtype H2
>
> WARNING 11 [file my_ligand_atomtypes.itp, line 13]:
> Overriding atomtype H1
>
> WARNING 12 [file my_ligand_atomtypes.itp, line 14]:
> Overriding atomtype OH
>
> WARNING 13 [file my_ligand_atomtypes.itp, line 15]:
> Overriding atomtype HO
>
> WARNING 14 [file my_ligand_atomtypes.itp, line 16]:
> Overriding atomtype OS
>
> WARNING 15 [file my_ligand_atomtypes.itp, line 17]:
> Overriding atomtype P
>
> WARNING 16 [file my_ligand_atomtypes.itp, line 18]:
> Overriding atomtype O2
>
> WARNING 17 [file my_ligand_atomtypes.itp, line 19]:
> Overriding atomtype CK
>
> WARNING 18 [file my_ligand_atomtypes.itp, line 20]:
> Overriding atomtype H5
>
> WARNING 19 [file my_ligand_atomtypes.itp, line 21]:
> Overriding atomtype NB
>
> WARNING 20 [file my_ligand_atomtypes.itp, line 22]:
> Overriding atomtype CB
>
> WARNING 21 [file my_ligand_atomtypes.itp, line 23]:
> Overriding atomtype N2
>
> WARNING 22 [file my_ligand_atomtypes.itp, line 24]:
> Overriding atomtype NC
>
> WARNING 23 [file my_ligand_atomtypes.itp, line 25]:
> Overriding atomtype CQ
> Generated 2211 of the 2211 non-bonded parameter combinations
> Generating 1-4 interactions: fudge = 0.5
> Generated 2211 of the 2211 1-4 parameter combinations
> Excluding 3 bonded neighbours molecule type 'A'
> Excluding 3 bonded neighbours molecule type 'B'
> Excluding 3 bonded neighbours molecule type 'NPD'
> Excluding 3 bonded neighbours molecule type 'IR3'
> Excluding 2 bonded neighbours molecule type 'SOL'
> "
> And I think it's harmless to ignore the warning here for the overriding
> atomtype. Am I correct? The image of ligand is in the link
Well, if you're overriding atom types, that means you're potentially changing
elements of the force field. That can cause catastrophic problems if you're not
careful. If these types are simply re-defining the same parameters already in
the force field, then yes it is safe, but also inherently unnecessary.
> http://postimg.org/image/fojbmkhrb/
Some of these ligands have extremely bizarre geometries, with H overlapping
heavy atoms. Something looks very wrong.
-Justin
> I would really appreciate for a help.
> Regards,
> Jennifer
> On Fri, Feb 13, 2015 at 10:45 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 2/13/15 2:47 PM, Jennifer Vo wrote:
>>
>>> Dear Justin,
>>> Please find the figure of output pdb file after minimizatrion.(I have sent
>>> in the previous email but it's pending... So I send it again)
>>>
>>>
>> The list doesn't accept attachments (if I had a nickel for every time I
>> said that...) so if you want to share images, upload them to a file-sharing
>> service and post the URL.
>>
>> Here is step by step how I built the system
>>> ### concatenate 2 chains and renumber the residues
>>> genconf -f AB.gro -o AB_renumber.gro -renumber
>>> ### redefine the small box the the proteins
>>> editconf -f AB_renumber.gro -o AB_box.gro -bt cubic -d 0.5 -c
>>> ### insert the first ligand
>>> gmx insert-molecules -f AB_box.gro -ci ligand1.gro -o AB_NADPH.pdb
>>> -nmol 1
>>> ### insert the second ligand
>>> gmx insert-molecules -f AB_NADPH.pdb -ci ir3_em.gro -o AB_NADPH_IR3.pdb
>>> -nmol 9 -seed -1
>>>
>>
>> OK, so "ligands" are actually just randomly inserted molecules, freely
>> floating in the solvent.
>>
>> ### redefine the box the the system
>>> editconf -f AB_NADPH_IR3.pdb -o AB_NADPH_IR3_box.pdb -bt cubic -d 1.0 -c
>>>
>>
>> Why is this necessary?
>>
>> ### adding water
>>> gmx solvate -cp AB_NADPH_IR3_box.pdb -cs spc216.gro -o
>>> AB_NADPH_IR3_solvate.pdb -p topol.top
>>> ### convert pdb to gro file
>>> editconf -f AB_NADPH_IR3_solvate.pdb -o AB_NADPH_IR3_solvate.gro
>>> ### adding ions
>>> grompp -f em_ion.mdp -c AB_NADPH_IR3_solvate.gro -p topol.top -o ions.tpr
>>> -maxwarn 27
>>>
>>
>> The use of -maxwarn 27 is alarming. Why are you trying to override 27
>> errors? This would be suspect #1 in diagnosing problems.
>>
>> -Justin
>>
>>
>> genion -s ions.tpr -o AB_NADPH_IR3_solvate_ions.gro -p topol.top -pname NA
>>> -np 24 -n index.ndx
>>>
>>> Many thanks for your help.
>>>
>>> On Fri, Feb 13, 2015 at 4:01 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>>
>>>> On 2/13/15 9:59 AM, Jennifer Vo wrote:
>>>>
>>>> Dear Justin,
>>>>> Many thanks for your kind answer. The output of minimization for
>>>>> Protein +
>>>>> 1 Ligand
>>>>> Steepest Descents converged to Fmax < 100 in 868 steps
>>>>> Potential Energy = -8.0409740e+06
>>>>> Maximum force = 8.3073639e+01 on atom 267747
>>>>> Norm of force = 3.5544858e+00
>>>>>
>>>>> The out for Protein + 2 ligands
>>>>> Steepest Descents converged to Fmax < 100 in 2165 steps
>>>>> Potential Energy = -6.2125650e+06
>>>>> Maximum force = 8.6047729e+01 on atom 263858
>>>>> Norm of force = 3.6529241e+00
>>>>>
>>>>> I don't see any failure. But when I use trjconv from Output gro file to
>>>>> pdb
>>>>> file, I see the ligands screwed up.
>>>>>
>>>>>
>>>> Again, please define what this means. How did you build the system? Can
>>>> you share an image?
>>>>
>>>> In case "The ligand files are both set up within different boxes, so
>>>>
>>>>> perhaps the construction of your system is incorrect somehow", how do I
>>>>> fix
>>>>> it? Do I have to change the final line of every ligand's topology file?
>>>>>
>>>>>
>>>> Well, assuming you're copying and pasting coordinates to construct the
>>>> system, if they're defined in different boxes, they're probably not going
>>>> to be where they should be when you define a third box with different
>>>> dimensions, unless you're using editconf to reposition in between.
>>>> Again,
>>>> you'll need to provide actual specifics of how you built the system
>>>> (step-by-step commands, please).
>>>>
>>>> -Justin
>>>>
>>>>
>>>> Which are
>>>>
>>>>>
>>>>> 1IR3 HAF 22 10.581 10.138 10.385
>>>>> 20.72517 20.72517 20.72517
>>>>> and
>>>>> 1NPD H8A 73 -0.376 0.292 -5.440
>>>>> 1.94588 0.88647 1.08377
>>>>>
>>>>> and the box of the System including Proteins + 2 ligands
>>>>>
>>>>> 23746NA NA79296 15.582 10.741 1.636
>>>>> 15.63000 15.63000 15.63000
>>>>>
>>>>> Many thanks in advance!
>>>>> Jennifer
>>>>>
>>>>>
>>>>> On Fri, Feb 13, 2015 at 3:44 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>>>
>>>>>
>>>>>
>>>>>> On 2/13/15 6:03 AM, Jennifer Vo wrote:
>>>>>>
>>>>>> Dear All,
>>>>>>
>>>>>>> I am running a simulation for a systems including two chains of
>>>>>>> proteins
>>>>>>> and two ligands using amber 99SB ff.
>>>>>>> My topol.top is
>>>>>>>
>>>>>>> #include "amber99sb.ff/forcefield.itp"
>>>>>>> #include "my_ligand_atomtypes.itp"
>>>>>>>
>>>>>>> ; Include chain topologies
>>>>>>> #include "A.itp"
>>>>>>> #ifdef POSRES
>>>>>>> #include "posre_A.itp"
>>>>>>> #endif
>>>>>>> #include "B.itp"
>>>>>>> #ifdef POSRES
>>>>>>> #include "posre_B.itp"
>>>>>>> #endif
>>>>>>>
>>>>>>> ; Include custom ligand topologies
>>>>>>> #include "npd.itp"
>>>>>>> #ifdef POSRES_LIG
>>>>>>> #include "posre_npd.itp"
>>>>>>> #endif
>>>>>>> ; Include custom ligand topologies
>>>>>>> #include "ir3_em.itp"
>>>>>>> ; Include water topology
>>>>>>> #include "amber99sb.ff/tip3p.itp"
>>>>>>>
>>>>>>> #ifdef POSRES_WATER
>>>>>>> ; Position restraint for each water oxygen
>>>>>>> [ position_restraints ]
>>>>>>> ; i funct fcx fcy fcz
>>>>>>> 1 1 1000 1000 1000
>>>>>>> #endif
>>>>>>> ; Include generic ion topology
>>>>>>> #include "amber99sb.ff/ions.itp"
>>>>>>>
>>>>>>> [ system ]
>>>>>>> ; Name
>>>>>>> BcSIRED in water
>>>>>>> [ molecules ]
>>>>>>> ; Compound #mols
>>>>>>> A 1
>>>>>>> B 1
>>>>>>> NPD 1
>>>>>>> IR3 9
>>>>>>> SOL 123406
>>>>>>> NA 24
>>>>>>>
>>>>>>> then I have my_ligand_atomtypes.itp
>>>>>>> [ atomtypes ]
>>>>>>> ;name bond_type mass charge ptype sigma epsilon
>>>>>>> Amb
>>>>>>> CA CA 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> H4 H4 0.00000 0.00000 A 2.51055e-01
>>>>>>> 6.27600e-02
>>>>>>> ;
>>>>>>> 1.41 0.0150
>>>>>>> HA HA 0.00000 0.00000 A 2.59964e-01
>>>>>>> 6.27600e-02
>>>>>>> ;
>>>>>>> 1.46 0.0150
>>>>>>> C C 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> O O 0.00000 0.00000 A 2.95992e-01
>>>>>>> 8.78640e-01
>>>>>>> ;
>>>>>>> 1.66 0.2100
>>>>>>> N N 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>> H H 0.00000 0.00000 A 1.06908e-01
>>>>>>> 6.56888e-02
>>>>>>> ;
>>>>>>> 0.60 0.0157
>>>>>>> N* N* 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>> CT CT 0.00000 0.00000 A 3.39967e-01
>>>>>>> 4.57730e-01
>>>>>>> ;
>>>>>>> 1.91 0.1094
>>>>>>> H2 H2 0.00000 0.00000 A 2.29317e-01
>>>>>>> 6.56888e-02
>>>>>>> ;
>>>>>>> 1.29 0.0157
>>>>>>> H1 H1 0.00000 0.00000 A 2.47135e-01
>>>>>>> 6.56888e-02
>>>>>>> ;
>>>>>>> 1.39 0.0157
>>>>>>> OH OH 0.00000 0.00000 A 3.06647e-01
>>>>>>> 8.80314e-01
>>>>>>> ;
>>>>>>> 1.72 0.2104
>>>>>>> HO HO 0.00000 0.00000 A 0.00000e+00
>>>>>>> 0.00000e+00
>>>>>>> ;
>>>>>>> 0.00 0.0000
>>>>>>> OS OS 0.00000 0.00000 A 3.00001e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.68 0.1700
>>>>>>> P P 0.00000 0.00000 A 3.74177e-01
>>>>>>> 8.36800e-01
>>>>>>> ;
>>>>>>> 2.10 0.2000
>>>>>>> O2 O2 0.00000 0.00000 A 2.95992e-01
>>>>>>> 8.78640e-01
>>>>>>> ;
>>>>>>> 1.66 0.2100
>>>>>>> CK CK 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> H5 H5 0.00000 0.00000 A 2.42146e-01
>>>>>>> 6.27600e-02
>>>>>>> ;
>>>>>>> 1.36 0.0150
>>>>>>> NB NB 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>> CB CB 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> N2 N2 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>> NC NC 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>> CQ CQ 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> ; IR3_GMX.top created by acpype (Rev: 403) on Wed Feb 4 11:55:46
>>>>>>> 2015
>>>>>>> ; Include forcefield parameters
>>>>>>> [ atomtypes ]
>>>>>>> ;name bond_type mass charge ptype sigma
>>>>>>> epsilon Amb
>>>>>>> C C 0.00000 0.00000 A 3.39967e-01
>>>>>>> 3.59824e-01
>>>>>>> ;
>>>>>>> 1.91 0.0860
>>>>>>> H H 0.00000 0.00000 A 1.06908e-01
>>>>>>> 6.56888e-02
>>>>>>> ;
>>>>>>> 0.60 0.0157
>>>>>>> N N 0.00000 0.00000 A 3.25000e-01
>>>>>>> 7.11280e-01
>>>>>>> ;
>>>>>>> 1.82 0.1700
>>>>>>>
>>>>>>> My first ligand gro file
>>>>>>> GRoups of Organic Molecules in ACtion for Science
>>>>>>> 73
>>>>>>> 1NPD OA22 1 -0.282 0.251 -5.719
>>>>>>> 1NPD OA23 2 -0.142 0.366 -5.542
>>>>>>> 1NPD OA24 3 -0.039 0.314 -5.771
>>>>>>> 1NPD P'A2 4 -0.145 0.285 -5.669
>>>>>>> 1NPD PA 5 -0.033 -0.056 -5.010
>>>>>>> 1NPD PN 6 -0.130 -0.245 -4.804
>>>>>>> 1NPD O3P 7 -0.126 -0.116 -4.893
>>>>>>> 1NPD N1A 8 -0.692 0.110 -5.840
>>>>>>> 1NPD N1N 9 -0.539 -0.355 -4.443
>>>>>>> 1NPD C2A 10 -0.613 0.000 -5.836
>>>>>>> ...
>>>>>>> 1NPD H8A 73 -0.376 0.292 -5.440
>>>>>>> 1.94588 0.88647 1.08377
>>>>>>>
>>>>>>> My second ligand gro file
>>>>>>>
>>>>>>> IR3_GMX.gro created by acpype (Rev: 403) on Wed Feb 4 11:55:46 2015
>>>>>>> 22
>>>>>>> 1IR3 CAA 1 10.182 10.576 10.387
>>>>>>> 1IR3 HAB 2 10.211 10.640 10.305
>>>>>>> 1IR3 HAA 3 10.075 10.577 10.396
>>>>>>> ....
>>>>>>> 1IR3 HAF 22 10.581 10.138 10.385
>>>>>>> 20.72517 20.72517 20.72517
>>>>>>>
>>>>>>> but the system can`t go under energy minimization. This is my em.mdp
>>>>>>>
>>>>>>> title = Minimization ; Title of run
>>>>>>> integrator = steep ; Algorithm (steep = steepest descent
>>>>>>> minimization)
>>>>>>> emtol = 1000.0 ; Stop minimization when the maximum
>>>>>>> force
>>>>>>> < 1000.0 kJ/mol
>>>>>>> emstep = 0.01 ; Energy step size
>>>>>>> nsteps = 500000 ; Maximum number of
>>>>>>> (minimization)
>>>>>>> steps to perform
>>>>>>> energygrps = Protein NPD IR3 ; Which energy group(s) to
>>>>>>> write
>>>>>>> to
>>>>>>> disk
>>>>>>> nstlist = 1 ; Frequency to update the neighbor
>>>>>>> list
>>>>>>> and long range forces
>>>>>>> cutoff-scheme = Verlet
>>>>>>> ns_type = grid ; Method to determine neighbor
>>>>>>> list
>>>>>>> (simple, grid)
>>>>>>> rlist = 1.0 ; Cut-off for making neighbor
>>>>>>> list
>>>>>>> (short range forces)
>>>>>>> coulombtype = PME ; Treatment of long range
>>>>>>> electrostatic interactions
>>>>>>> rcoulomb = 1.0 ; long range electrostatic
>>>>>>> cut-off
>>>>>>> rvdw = 1.0 ; long range Van der Waals
>>>>>>> cut-off
>>>>>>> pbc = xyz ; Periodic Boundary Conditions
>>>>>>>
>>>>>>> I change emtol from 1000, then 500, then 100. No error generated but
>>>>>>> the
>>>>>>> pdb output file goes wrong with the ligands. If I do the same
>>>>>>> procedure
>>>>>>> with seperated ligand (only one [ atomtypes] in
>>>>>>> my_ligand_atomtypes.itp),
>>>>>>> things goes well . Could you please help me where is the problem?
>>>>>>> Many thanks in advance.
>>>>>>>
>>>>>>>
>>>>>>> You'll have to be much more specific than "goes wrong with the
>>>>>> ligands."
>>>>>> What's happening? Does EM fail or is the output just somehow screwed
>>>>>> up?
>>>>>> The ligand files are both set up within different boxes, so perhaps the
>>>>>> construction of your system is incorrect somehow, but again, without
>>>>>> specifics, I'm just guessing.
>>>>>>
>>>>>> -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
>>>>>>
>>>>>> ==================================================
>>>>>> --
>>>>>> Gromacs Users mailing list
>>>>>>
>>>>>> * Please search the archive at http://www.gromacs.org/
>>>>>> Support/Mailing_Lists/GMX-Users_List before posting!
>>>>>>
>>>>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>>>>
>>>>>> * For (un)subscribe requests visit
>>>>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>>>>> send a mail to gmx-users-request at gromacs.org.
>>>>>>
>>>>>>
>>>>>> --
>>>> ==================================================
>>>>
>>>> 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
>>>>
>>>> ==================================================
>>>> --
>>>> Gromacs Users mailing list
>>>>
>>>> * Please search the archive at http://www.gromacs.org/
>>>> Support/Mailing_Lists/GMX-Users_List before posting!
>>>>
>>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>>
>>>> * For (un)subscribe requests visit
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>>>> send a mail to gmx-users-request at gromacs.org.
>>>>
>>>>
>> --
>> ==================================================
>>
>> 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
>>
>> ==================================================
>> --
>> Gromacs Users mailing list
>>
>> * Please search the archive at http://www.gromacs.org/
>> Support/Mailing_Lists/GMX-Users_List before posting!
>>
>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>
>> * For (un)subscribe requests visit
>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>> send a mail to gmx-users-request at gromacs.org.
>>
--
==================================================
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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