[gmx-users] Free energy change with harmonic restraints

[Natalie Nguyen]

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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