[gmx-users] Free energy change with harmonic restraints

Tue Jul 14 16:56:36 CEST 2015

Dear Natalie,

Feel well!

If you'll have questions feel free to ask.

Best regards,
Asaf

Quoting Natalie Nguyen <nguyenn at wittenberg.edu>:

> Dear Asaf,
>
> I was ill this weekend but I a better now!
> I will try to simulate the system as the way as you instructed and  
> will let you know my results!
>
> Thank you again,
> Natalie
>
> ________________________________________
> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se  
> <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of  
> asaffarhi at post.tau.ac.il <asaffarhi at post.tau.ac.il>
> Sent: Sunday, July 12, 2015 2:54 AM
> To: gromacs.org_gmx-users at maillist.sys.kth.se
> Subject: Re: [gmx-users] Free energy change with harmonic restraints
>
> Dear Natalie,
>
> The weekend was good. Thanks. I hope that you have a great weekend too.
>
> If you manage to simulate the system with restraints (A) and without
> restraints (B) you can calculate the free energy difference between
> A/B to a system in which the ligand is not interacting with the
> environment (protein and solvent) at all. The free energy associated
> with the restraints when the ligand is not interacting via VDW and
> electrostatic interactions with the environment can be calculated with
> the analytic expressions.
>
> In summary you can calculate Delta F_{A->A'} and F_{B->B'} where A'
> and B' are when the ligand is not interacting via VDW and
> electrostatic interactions with the environment without and with
> restraints respectively. This can be calculated by TI, Bar etc. Then
> there is to calculate F_{B'->B''} where this free energy difference is
> given by the analytic equations. F_B''=F_A' since it's a system in
> which the ligand is not interacting with the environment (protein and
> solvent) at all. Thus you can calculate F_{A->A'} and F_{B->B''} and
> obtain F_{A->B}.
>
> I hope it helps.
>
> Best regards,
> Asaf
>
>
>
> Quoting Natalie Nguyen <nguyenn at wittenberg.edu>:
>
>> Dear Asaf,
>>
>> I hope you have had a great weekend!
>> I have tried applying TI with restraint-lambdas to measure the free
>> energy difference of applying restraints without success (no dhdl
>> files were being outputted). The tutorial in the link provided by
>> Hannes Loeffler I have looked over before, but my intentions are not
>> measuring the free energy change of binding.
>> I would like to know in more detail on how to approach this.
>>
>> Much appreciated,
>> Natalie
>>
>> ________________________________________
>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se
>> <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of
>> asaffarhi at post.tau.ac.il <asaffarhi at post.tau.ac.il>
>> Sent: Thursday, July 09, 2015 5:58 PM
>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>> Subject: Re: [gmx-users] Free energy change with harmonic restraints
>>
>> Dear Natalie,
>>
>> What I can say is that e.g Thermodynamic Integration should give the
>> free energy difference of this transformation. If you are interested
>> in the free energy of binding the link provided to you by Hannes
>> Loeffler may be useful. Also, for such a k value in case you will need
>> analytic equations it will be better to use the exact equations (the
>> equations in this link are approximate). I'll supply an exact equation
>> if you'll need for the free energy of a dihedral harmonic term.
>>
>> I hope to have more time next week and give more details (the weekend
>> starts here).
>>
>> Best regards,
>> Asaf
>>
>> I hope to have more time next week and to try
>>
>> Quoting Natalie Nguyen <nguyenn at wittenberg.edu>:
>>
>>> Dear Asaf,
>>>
>>> Thank you again for putting in the time to respond to me so quickly.
>>> What I have been trying to do was start from a system that is not
>>> restrained and grow the restraints onto the ligand, measuring the
>>> change in free energy of this. The harmonic restraints used are that
>>> of the umbrella pull code with a force constant of k= 1000
>>> kJ/mol*nm^2. It is mentioned In the Gromacs manual for mdp options
>>> that the pull code can be controlled with "restraint-lambdas", but
>>> there is not much detail other than this. I imagine that lambda =0
>>> would represent a nonexistent potential with k= 0 and at lambda = 1
>>> a full strength potential would be imposed.
>>> Please feel free to ask me to add more detail!
>>>
>>> Warm regards,
>>> Natalie
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se
>>> <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of
>>> asaffarhi at post.tau.ac.il <asaffarhi at post.tau.ac.il>
>>> Sent: Thursday, July 09, 2015 10:38 AM
>>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>>> Subject: Re: [gmx-users] Free energy change with harmonic restraints
>>>
>>> Dear Natalie,
>>>
>>> You are welcome.
>>> Could you please explain in more detail so maybe I can help?
>>> Do you want to change the strength of the restraints and measure the
>>> free energy difference associated with this change?
>>>
>>> Thanks. p.s there is also http://arxiv.org/pdf/1307.1620v7.pdf with
>>> the same equations.
>>>
>>> Best regards,
>>> Asaf
>>>
>>> Quoting Natalie Nguyen <nguyenn at wittenberg.edu>:
>>>
>>>> Dear Asaf,
>>>>
>>>> Thank you for the quick reply!
>>>>
>>>> I was wondering if it was possible to use thermodynamic integration
>>>> to represent growing harmonic restraints aside from using an
>>>> analytical method.
>>>>
>>>> I will cite this article most definitely!
>>>>
>>>> Natalie Nguyen
>>>>
>>>> ________________________________________
>>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se
>>>> <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of
>>>> asaffarhi at post.tau.ac.il <asaffarhi at post.tau.ac.il>
>>>> Sent: Thursday, July 09, 2015 7:45 AM
>>>> To: gromacs.org_gmx-users at maillist.sys.kth.se
>>>> Subject: Re: [gmx-users] Free energy change with harmonic restraints
>>>>
>>>> Dear Natalie,
>>>>
>>>> You have in
>>>>
>>>> http://xxx.tau.ac.il/pdf/1502.07196v3.pdf
>>>>
>>>> exact free energy of harmonic covalent bond and bond angle terms (or
>>>> restrains). See Eqs. (2) and (3).
>>>>
>>>> There are also previous studies in the references there.
>>>>
>>>> For the dihedral term I assume it can also be calculated exactly (I
>>>> might upload it).
>>>>
>>>> There is also to think if there are other contributions.
>>>>
>>>> If you are using it please cite.
>>>>
>>>> Best regards,
>>>> Asaf
>>>>
>>>>
>>>> Quoting Natalie Nguyen <nguyenn at wittenberg.edu>:
>>>>
>>>>> Dear all,
>>>>>
>>>>>
>>>>> I am trying to measure the free energy change associated with
>>>>> adding/removing harmonic restraints imposed on a ligand that is
>>>>> attached to a protein. Is there any way to set this up?
>>>>>
>>>>>
>>>>> Thank you ahead of time!
>>>>>
>>>>>
>>>>> Natalie Nguyen
>>>>> --
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>>>>
>>>>
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