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

Ozbil, Mehmet m.ozbil at umiami.edu
Thu Jan 30 16:26:29 CET 2014


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