[gmx-users] free energy calculations for reference state for constant pH MD simulations...

bipin singh bipinelmat at gmail.com
Thu Jan 30 18:19:41 CET 2014


I think the corresponding dihedral (involving the HE2 atom) also need to be
changed in the B state during the transformation.


On Thu, Jan 30, 2014 at 9:48 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 1/30/14, 11:12 AM, bipin singh wrote:
>
>> The protonated and deprotonated states will differ only in terms of
>> presence or absence of hydrogens, thus in B state only that hydrogen atom
>> which is intended to be transformed from protonated to deprotonated state
>> will be altered in the terms of electrostatic and vdw parameters.
>>
>>
> Incorrect.  The atom types and charges for the whole carboxylate moiety
> are affected by the removal of the proton.  Only H becomes a dummy atom,
> but the C and both O atoms of the resulting COO- group will be different
> depending on protonation state.  See GLU/GLUH in aminoacids.rtp.
>
> -Justin
>
>
>
>> On Thu, Jan 30, 2014 at 8:55 PM, Ozbil, Mehmet <m.ozbil at umiami.edu>
>> wrote:
>>
>>  I see Bipin,
>>>
>>> Thanks. One quick question though, am I going to change the charges to
>>> zero or all atoms to DUM atoms for all the atoms in B state or just for
>>> the
>>> hydrogen that will be transferred between the states (the atom where the
>>> B
>>> state was missing before):
>>>
>>> 16   opls_270     77    GLU    HE2      5       0.45      1.008
>>>
>>> Thanks again.
>>>
>>> Mehmet
>>>
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <
>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of bipin
>>> singh <bipinelmat at gmail.com>
>>> Sent: Wednesday, January 29, 2014 10:46 PM
>>> To: Discussion list for GROMACS users
>>> Subject: Re: [gmx-users] free energy calculations for reference state for
>>> constant pH MD simulations...
>>>
>>> You have to define the B state parameters for your deprotonated state
>>> explicitly.
>>>
>>> The following line in your topology does not have the parameters for the
>>> B
>>> state.
>>>
>>> 16   opls_270     77    GLU    HE2      5       0.45      1.008
>>>
>>> You have to set the charges zero in the B state (if you want to consider
>>> the change in electrostatic term only during deprotonation) or else
>>> change
>>> it to DUM atom (if you want to change both the vdw and electrostatics
>>> terms
>>> during deprotonation).
>>>
>>>
>>> On Wed, Jan 29, 2014 at 8:15 PM, Ozbil, Mehmet <m.ozbil at umiami.edu>
>>> wrote:
>>>
>>>
>>>> Thanks Bipin for the reply.
>>>>
>>>> I went through the Gromacs manual, and thought that I managed to
>>>> incorporate two states (protonated and deprotonated) in my topology
>>>> file.
>>>> Can anyone who has done it before tell me if I  defined both A and B
>>>>
>>> states
>>>
>>>> correctly in my .top file.
>>>>
>>>> ;
>>>> ;       File 'GLUA_prot_OPLS_p.top' was generated
>>>> ;       By user: onbekend (0)
>>>> ;       On host: onbekend
>>>> ;       At date: Tue Jan 28 13:49:17 2014
>>>> ;
>>>> ;       This is a standalone topology file
>>>> ;
>>>> ;       It was generated using program:
>>>> ;       pdb2gmx - VERSION 4.5.4
>>>> ;
>>>> ;       Command line was:
>>>> ;       /home/apps/fas/Apps/Gromacs/gromacs-4.5.4-intel/bin//pdb2gmx -f
>>>> GLUA_prot_OPLS.pdb -p GLUA_prot_OPLS_p.top -o GLUA_prot_OPLS_p.gro
>>>> -inter
>>>> ;
>>>> ;       Force field was read from the standard Gromacs share directory.
>>>> ;
>>>>
>>>> ; Include forcefield parameters
>>>> #include "oplsaa.ff/forcefield.itp"
>>>>
>>>> [ moleculetype ]
>>>> ; Name            nrexcl
>>>> Protein_chain_A     3
>>>>
>>>> [ atoms ]
>>>> ;   nr       type  resnr residue  atom   cgnr     charge       mass
>>>>
>>>   typeB
>>>
>>>>     chargeB      massB
>>>> ; residue  77 GLU rtp GLUH q  0.0
>>>>       1   opls_287     77    GLU      N      1       -0.3    14.0067
>>>> opls_287   -0.3       14.0067
>>>>       2   opls_290     77    GLU     H1      1       0.33      1.008
>>>> opls_290    0.33       1.008
>>>>       3   opls_290     77    GLU     H2      1       0.33      1.008
>>>> opls_290    0.33       1.008
>>>>       4   opls_290     77    GLU     H3      1       0.33      1.008
>>>> opls_290    0.33       1.008
>>>>       5   opls_299     77    GLU     CA      1       0.15     12.011
>>>> opls_299    0.15      12.011
>>>>       6   opls_140     77    GLU     HA      1       0.06      1.008
>>>> opls_140    0.06       1.008
>>>>       7   opls_136     77    GLU     CB      2      -0.12     12.011
>>>> opls_136   -0.12      12.011
>>>>       8   opls_140     77    GLU    HB1      2       0.06      1.008
>>>> opls_140    0.06       1.008
>>>>       9   opls_140     77    GLU    HB2      2       0.06      1.008
>>>> opls_140    0.06       1.008
>>>>      10   opls_136     77    GLU     CG      3      -0.12     12.011
>>>> opls_136   -0.12      12.011
>>>>      11   opls_140     77    GLU    HG1      3       0.06      1.008
>>>> opls_140    0.06       1.008
>>>>      12   opls_140     77    GLU    HG2      3       0.06      1.008
>>>> opls_140    0.06       1.008
>>>>      13   opls_267     77    GLU     CD      4       0.52     12.011
>>>> opls_267    0.52      12.011
>>>>      14   opls_269     77    GLU    OE1      4      -0.44    15.9994
>>>> opls_269   -0.44      15.9994
>>>>      15   opls_268     77    GLU    OE2      5      -0.53    15.9994
>>>> opls_268   -0.53      15.9994
>>>>      16   opls_270     77    GLU    HE2      5       0.45      1.008
>>>>      17   opls_271     77    GLU      C      6        0.7     12.011
>>>> opls_271    0.7       12.011
>>>>      18   opls_272     77    GLU     O1      6       -0.8    15.9994
>>>> opls_272   -0.8       15.9994
>>>>      19   opls_272     77    GLU     O2      6       -0.8    15.9994
>>>> opls_272   -0.8       15.9994
>>>>
>>>> [ bonds ]
>>>> ;  ai    aj funct            c0            c1            c2
>>>>  c3
>>>>      1     2     1
>>>>      1     3     1
>>>>      1     4     1
>>>>      1     5     1
>>>>      5     6     1
>>>>      5     7     1
>>>>      5    17     1
>>>>      7     8     1
>>>>      7     9     1
>>>>      7    10     1
>>>>     10    11     1
>>>>     10    12     1
>>>>     10    13     1
>>>>     13    14     1
>>>>     13    15     1
>>>>     15    16     1
>>>>     17    18     1
>>>>     17    19     1
>>>>
>>>> [ pairs ]
>>>> ;  ai    aj funct            c0            c1            c2
>>>>  c3
>>>>      1     8     1
>>>>      1     9     1
>>>>      1    10     1
>>>>      1    18     1
>>>>      1    19     1
>>>>      2     6     1
>>>>      2     7     1
>>>>      2    17     1
>>>>      3     6     1
>>>>      3     7     1
>>>>      3    17     1
>>>>      4     6     1
>>>>      4     7     1
>>>>      4    17     1
>>>>      5    11     1
>>>>      5    12     1
>>>>      5    13     1
>>>>      6     8     1
>>>>      6     9     1
>>>>      6    10     1
>>>>      6    18     1
>>>>      6    19     1
>>>>      7    14     1
>>>>      7    15     1
>>>>   7    18     1
>>>>      7    19     1
>>>>      8    11     1
>>>>      8    12     1
>>>>      8    13     1
>>>>      8    17     1
>>>>      9    11     1
>>>>      9    12     1
>>>>      9    13     1
>>>>      9    17     1
>>>>     10    16     1
>>>>     10    17     1
>>>>     11    14     1
>>>>     11    15     1
>>>>     12    14     1
>>>>     12    15     1
>>>>     14    16     1
>>>>
>>>> [ angles ]
>>>> ;  ai    aj    ak funct            c0            c1            c2
>>>>     c3
>>>>      2     1     3     1
>>>>      2     1     4     1
>>>>      2     1     5     1
>>>>      3     1     4     1
>>>>      3     1     5     1
>>>>      4     1     5     1
>>>>      1     5     6     1
>>>>      1     5     7     1
>>>>      1     5    17     1
>>>>      6     5     7     1
>>>>      6     5    17     1
>>>>      7     5    17     1
>>>>      5     7     8     1
>>>>      5     7     9     1
>>>>      5     7    10     1
>>>>      8     7     9     1
>>>>      8     7    10     1
>>>>      9     7    10     1
>>>>      7    10    11     1
>>>>      7    10    12     1
>>>>      7    10    13     1
>>>>     11    10    12     1
>>>>     11    10    13     1
>>>>     12    10    13     1
>>>>     10    13    14     1
>>>>     10    13    15     1
>>>>     14    13    15     1
>>>>   13    15    16     1
>>>>      5    17    18     1
>>>>      5    17    19     1
>>>>     18    17    19     1
>>>>
>>>> [ dihedrals ]
>>>> ;  ai    aj    ak    al funct            c0            c1            c2
>>>>           c3            c4            c5
>>>>      2     1     5     6     3
>>>>      2     1     5     7     3
>>>>      2     1     5    17     3
>>>>      3     1     5     6     3
>>>>      3     1     5     7     3
>>>>      3     1     5    17     3
>>>>      4     1     5     6     3
>>>>      4     1     5     7     3
>>>>      4     1     5    17     3
>>>>      1     5     7    10     3    dih_GLU_chi1_N_C_C_C
>>>>     17     5     7    10     3    dih_GLU_chi1_C_C_C_CO
>>>>      1     5     7     8     3
>>>>      1     5     7     9     3
>>>>      6     5     7     8     3
>>>>      6     5     7     9     3
>>>>      6     5     7    10     3
>>>>     17     5     7     8     3
>>>>     17     5     7     9     3
>>>>      1     5    17    18     3
>>>>      1     5    17    19     3
>>>>      6     5    17    18     3
>>>>      6     5    17    19     3
>>>>      7     5    17    18     3
>>>>      7     5    17    19     3
>>>>      5     7    10    11     3
>>>>      5     7    10    12     3
>>>>      5     7    10    13     3
>>>>      8     7    10    11     3
>>>>      8     7    10    12     3
>>>>      8     7    10    13     3
>>>>      9     7    10    11     3
>>>>      9     7    10    12     3
>>>>      9     7    10    13     3
>>>>      7    10    13    14     3
>>>>      7    10    13    15     3
>>>>     11    10    13    14     3
>>>>     11    10    13    15     3
>>>>     12    10    13    14     3
>>>>     12    10    13    15     3
>>>>     10    13    15    16     3    dih_sidechain_COOH_C_C_O_H
>>>>    14    13    15    16     3    dih_sidechain_COOH_O_C_O_H
>>>>
>>>> [ dihedrals ]
>>>> ;  ai    aj    ak    al funct            c0            c1            c2
>>>>           c3
>>>>      5    18    17    19     1    improper_O_C_X_Y
>>>>     10    14    13    15     1    improper_O_C_X_Y
>>>>
>>>> ; Include Position restraint file
>>>> #ifdef POSRES
>>>> #include "posre.itp"
>>>> #endif
>>>>
>>>> ; Include water topology
>>>> #include "oplsaa.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 topology for ions
>>>> #include "oplsaa.ff/ions.itp"
>>>>
>>>> [ system ]
>>>> ; Name
>>>> Protein in water
>>>>
>>>> [ molecules ]
>>>> ; Compound        #mols
>>>> Protein_chain_A     1
>>>> SOL              4135
>>>>
>>>>
>>>> Thanks,
>>>> Mehmet
>>>>
>>>>
>>>>
>>>> ________________________________________
>>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <
>>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of bipin
>>>> singh <bipinelmat at gmail.com>
>>>> Sent: Tuesday, January 28, 2014 2:46 AM
>>>> To: Discussion list for GROMACS users
>>>> Subject: Re: [gmx-users] free energy calculations for reference state
>>>> for
>>>> constant pH MD simulations...
>>>>
>>>> See the section  "5.7.4 Topologies for free energy calculations" in
>>>>
>>> Gromacs
>>>
>>>> 4.6.5 manual.
>>>>
>>>>
>>>>
>>>> On Tue, Jan 28, 2014 at 3:09 AM, Ozbil, Mehmet <m.ozbil at umiami.edu>
>>>>
>>> wrote:
>>>
>>>>
>>>>  Hello,
>>>>>
>>>>> I am trying to run constant pH MD with GROMACS, and started with the TI
>>>>> free energy calculations. I am following Justin Lemkul`s free energy
>>>>> calculation tutorial, and assuming that the free energy calculations
>>>>>
>>>> will
>>>
>>>> be similar to calculate the protonation energy of titratable amino
>>>>>
>>>> acids
>>>
>>>> such as GLU or HIS.
>>>>>
>>>>> My question is that, while scanning the lambda values for the free
>>>>>
>>>> energy
>>>
>>>> calculations do I need to define both protonated and deprotonated
>>>>>
>>>> states
>>>
>>>> of
>>>>
>>>>> GLU in the same .top and .pdb file, or I just use one .top and one .pdb
>>>>> file and by changing the lambda values from 0.0 to 1.0 it does the
>>>>> deprotonation itself. If I need to incorporate the two states in one
>>>>>
>>>> .top
>>>
>>>> and .pdb file can anyone help with how to do that?
>>>>>
>>>>> Thanks,
>>>>> Mehmet Ozbil
>>>>> --
>>>>> Gromacs Users mailing list
>>>>>
>>>>> * Please search the archive at
>>>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>>>>> posting!
>>>>>
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>>>>> send a mail to gmx-users-request at gromacs.org.
>>>>>
>>>>>
>>>>
>>>>
>>>> --
>>>>
>>>>
>>>>
>>>> *--------------------Thanks and Regards,Bipin Singh*
>>>> --
>>>> Gromacs Users mailing list
>>>>
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>>>
>>>
>>> --
>>>
>>>
>>>
>>> *--------------------Thanks and Regards,Bipin Singh*
>>> --
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>>
>>
>>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 601
> 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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-- 



*--------------------Thanks and Regards,Bipin Singh*


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