Thanks Thomas !
I have just the last particular question.
In spite the fact that the very last part of the ligand decoupling from
the receptor (using restraints):
dAr
(R)s***(L)v----->(R)s + (L)v
(i.e. calculation of the free energy change connected with the
"anihilation" of the restraints
which are applied on already non-interacting (vdw/el) ligand) is possible
to calculate analytically,
I would like to verify it numerically by TI with this setup:
V0 = Receptor + Ligand (in water) where all the ligand atoms are DUMMY
atoms.
Ligand is restrained in V0 with target restraints (defined in the RST file)
(ifsc=0, scmask='', crgmask='')
dvdl_norest=0
V1 = Receptor + Ligand (in water) where all the ligand atoms are DUMMY
atoms.
Ligand is free to move in V1 (no restraints)
(ifsc=0, scmask='', crgmask='')
dvdl_norest=0
Might it be correct for the given purpose ?
Thank you very much again !
Best wishes,
Marek
Dne Wed, 09 May 2012 17:08:52 +0200 <steinbrt.rci.rutgers.edu> napsal/-a:
> Hi,
>
>> Regarding the scaling constant (which "preventively" scale restraints)
>> when SC pot. are used: 1/lambda versus 1/(1-lambda) maybe it is not
>> the "full typo" as this is probably dependent on simulated process. For
>> the ligand "disappearing" scaling constant
>> is 1/(1-lambda) for the opposite process (appearing) perhaps 1/lambda is
>> used. This would correspond to the disappearing/appearing
>> SF-potentials where in case of disappearing multiplicative constant
>> (1-lambda) is used and in case of appearing it is just lambda.
>
> True, maybe that was my idea when writing it. However, I think only the
> setup in which whole restrained ligands disappear has ever been used.
>
>> #1 - appearing of the restraints while ligand is fully (vdw/el)
>> interacting with receptor during this process
>>
>> Here I would use this approach:
>>
>> V0 = Receptor + Ligand (in water)
>> no restraint is applied in V0 ( ifsc=0, scmask='',crgmask='' )
>> dvdl_norest=0
>>
>>
>> V1 = Receptor + Ligand (in water)
>> Ligand is restrained in V1 with target restraints (defined in the RST
>> file) (ifsc=0, scmask='',crgmask='')
>> dvdl_norest=0
>
> yes, that is how I would do it. This linearly increases the restraint
> strength with lambda, which is what you want.
>
>> #2 Decoupling (vdw/el) the fully restrained ligand.
>>
>> Here I would use this setup:
>>
>> V0 = Receptor + Ligand (in water)
>> Ligand is restrained in V0 with target restraints (defined in the RST
>> file) (ifsc=1, scmask=':LIGAND',crgmask='')
>> dvdl_norest=1
>>
>>
>> V1 = just Receptor (in water)
>> ( ifsc=1, scmask='',crgmask='' )
>> dvdl_norest=1
>>
>
> that is also right, but I think dvdl_norest can be left out in V1, it has
> no real effect there. It is necessary in V0. In this setup, the ligand
> will decouple, but will still be restrained with unchanged strength.
>
>> Anyway the second possibility for V1 might be here:
>>
>> V1 = Receptor + Ligand (in water) where all the ligand atoms are DUMMY
>> atoms.
>> Ligand is restrained in V1 with target restraints (defined in the RST
>> file) (ifsc=1, scmask=':LIGAND' or scmask='' ???, crgmask='')
>> dvdl_norest=1
>>
>
> No, that is not useful. Dummy atoms and softcore are mutually exclusive
> ways to do the same thing and they cannot be mixed like this. Stick to
> the
> first way you suggested.
>
> Kind Regards,
>
> Thomas
>
> Dr. Thomas Steinbrecher
> formerly at the
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
>
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Received on Wed May 09 2012 - 09:00:02 PDT
