I have never used TI or FEP. I thought I can use umbrella sampling
method to generate PMF profile and calculate the binding free energy.
TI, we must have two ligand and we can calculate the relative free
energy?
Can I use TI for calculating the binding free energy for the single
solute?
Thanks
Rajesh
On Thu, 10 Mar 2011 09:45:41 -0500
Carlos Simmerling <carlos.simmerling.gmail.com> wrote:
> it still isn't clear what you want to do. why use umbrella sampling
>for
> this, instead of TI or FEP?
>
> On Wed, Mar 9, 2011 at 1:55 PM, Rajesh Raju
> <rajesh.raju.mail.chem.tamu.edu>wrote:
>
>> Dear Carlos,
>>
>> Thank you very much for your reply. I have attached the receptor
>>molecule
>> structure with this email. I would like to studnt binding free
>>energy of
>> small solutes like benzene. I have shown the reaction coordinate. I
>>want to
>> generate aPMF profile for the inclusion of the solute molecules into
>>this
>> receptor. I can do the umbrella sampling in two different ways. One
>>way is
>> to make the coordinate and tolopoly files for different distance
>>restraint
>> and do umbrella sampling. The advantage is the dist_vs_time value
>>will start
>> from the closet value correspond to the distant constraint value.
>>Second way
>> is to keep the solute and receptor molecules at same configuration
>>and do
>> individual simulations corresponding to the different distance
>>constraint
>> value. Would both give the same PMF profile ? If different why and
>>which is
>> the best approach?
>>
>> Thanking you in advance
>> Rajesh
>>
>>
>>
>>
>> On Wed, 9 Mar 2011 07:04:24 -0500
>> Carlos Simmerling <carlos.simmerling.gmail.com> wrote:
>>
>>> you haven't made it clear what you're trying to calculate. Are you
>>> following
>>> a procedure shown to work well in a peer-reviewed article? I suspect
>>>that
>>> what you want to do is quite challenging. Keep in mind that umbrella
>>> sampling works well ONLY if the reaction coordinate you choose is
>>>the one
>>> responsible for the relevant energy changes, and you must be able to
>>>fully
>>> sample over motions in all of the other degrees of freedom in each
>>>of the
>>> umbrella windows. I suspect that at a fixed distance you will find
>>>it
>>> difficult to properly sample over all other motions (such as side
>>>chains,
>>> ligand flexibility, etc.
>>>
>>> given that, I'm not sure quite what you're asking. It seems that you
>>>have
>>> different numbers of waters. you can adjust the water buffer length
>>>in
>>> leap
>>> when you build the molecule- it might require trial and error.
>>>
>>> during your umbrella runs, make sure that you have overlap in the
>>> distribution of distances (histogram them) between all neighboring
>>> windows.
>>> any gaps will result in errors in free energy profile.
>>>
>>>
>>>
>>> On Tue, Mar 8, 2011 at 6:21 PM, Rajesh Raju
>>> <rajesh.raju.mail.chem.tamu.edu>wrote:
>>>
>>> Dear Amber users,
>>>>
>>>> I am planning to do an umbrella sampling on one of the receptor
>>>> molecule. I used the distance between the center of masses of the
>>>> receptor and ligand molecule as constraint. My doubts are:
>>>>
>>>> [1] Do I need to make different coordinate files for the complex,
>>>> corresponding to the distance between the center of masses of the
>>>>two
>>>> molecules? or Can I use the same coordinate file for all individual
>>>> simulations of the different windows?
>>>>
>>>> [2] changing the distance variable in the 'DISANG=dist.dat' file to
>>>> different distance values corresponding to different windows, and
>>>>keep
>>>> the same coordinate files with center of masses of two molecules
>>>>close
>>>> to zero, would be the same effect as that of the doing different
>>>> window simulations, making new coord files corresponding to the
>>>> umbrella sampling distance.
>>>>
>>>> So far I proceeded with the second approach:
>>>>
>>>> I made the new coordinates corresponding to different R variables
>>>>from
>>>> 0.5 to 10 ..20 windows. and made parameter and coordinate files for
>>>> the individual windows..The number of water molecules are slightly
>>>> different....
>>>>
>>>> Which is the best way?
>>>>
>>>> Thanks
>>>> Rajesh
>>>>
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Received on Thu Mar 10 2011 - 10:00:04 PST
