[gmx-users] binding free energy with gromacs2016

[Justin Lemkul]

On 11/8/16 11:00 AM, Qasim Pars wrote:
> Dear users,
>
> Hope someone will answer the questions in my previous mail.
>
> Thanks in advance,
>
>> On 6 Nov 2016, at 23:48, Qasim Pars <qasimpars at gmail.com> wrote:
>>
>> Dear users,
>>
>> I will try to do binding free energy calculation using GROMACS2016 but I am confused a little bit about the preparation of  the input files. I have a few questions:
>>
>> 1) There are below lines to apply a harmonic distance restraint in the mdp files of the binding free energy tutorial http://www.alchemistry.org/wiki/GROMACS_4.6_example:_n-phenylglycinonitrile_binding_to_T4_lysozyme
>>
>> pull           = umbrella
>> pull_geometry  = distance
>> pull_dim       = Y Y Y
>> pull_start     = no
>> pull_init1     = 0.654
>> pull_ngroups   = 1
>> pull_group0    = a_1391
>> pull_group1    = a_2615
>> pull_k1        = 0.0   ; kJ*mol^(-1)*nm^(-2)
>> pull_kB1       = 4184  ; kJ*mol^(-1)*nm^(-2)
>>
>> Question 1: Instead of those lines I would like to use the [ intermolecular_interactions ] section in the topology file with GROMACS2016. Could you please tell me what to write the [ intermolecular_interactions ] section?
>>

Why?  The pull code is modulated in a lambda-dependent fashion, which is 
probably part of the tutorial and computed free energy.

>> 2) complex.top file of the tutorial is as follows:
>> ; Include forcefield parameters
>> #include "amber99sb-ildn.ff/forcefield.itp"
>>
>> [ atomtypes ]
>> ;name  bond_type          mass        charge  ptype   sigma      epsilon
>> c3            c3          0.0000      0.0000  A   3.39967e-01  4.57730e-01
>> dc3           c3          0.0000      0.0000  A   0.00000e+00  0.00000e+00
>> ....
>>
>> Question 2: Why all values (sigma and epsilon) of dc3 are zero?
>>

This is effectively a dummy atom, used in transforming the ligand.

>> [ nonbond_params ]
>> ; i  j    func  sigma           epsilon
>> c3   c3    1     3.3996700e-01   4.5773000e-01
>> dc3  dc3   1     3.3996700e-01   4.5773000e-01
>> ....
>> Question 3: Why all values of dc3 aren't zero?
>>

These are pair-specific interactions.

>> [ angle_restraints ]
>> ; ai     aj    ak    al    type     thA      kA         multA      thB      kB         multB
>>  1393   1391   2615  1391  1        88.8     0.00       1          88.8     41.84   1
>>  1391   2615   2614  2615  1        32.9     0.00       1          32.9     41.84   1
>>
>> [ dihedral_restraints ]
>> ; ai    aj    ak    al       type   phiA     dphiA   kA          phiB     dphiB   kB
>>   1410  1393  1391  2615     1      -159.7  0.0      0.00        -159.7   0.0     41.84
>>   1393  1391  2615  2614     1      122.6   0.0      0.00         122.6   0.0     41.84
>>   1391  2615  2614  2610     1      12.8    0.0      0.00          12.8   0.0     41.84
>> .....
>> Question 4: Do I still need to put those ligand parameters (dc3, [ angle_restraints ], [ dihedral_restraints ] ... ) into the topology file to use with GROMACS2016?
>>

There is no version-dependent difference here with respect to the topology.

-Justin

>> I read section 5.4.2 and 6.1 of the GROMACS2016 manual but I couldn't understand how to prepare the input files.
>> --
>> Qasim Pars

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

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

==================================================