Re: [AMBER] Umbrella sampling coordinate question

From: Rajesh Raju <>
Date: Thu, 10 Mar 2011 11:45:22 -0600

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

Can I use TI for calculating the binding free energy for the single


On Thu, 10 Mar 2011 09:45:41 -0500
  Carlos Simmerling <> wrote:
> it still isn't clear what you want to do. why use umbrella sampling
> this, instead of TI or FEP?
> On Wed, Mar 9, 2011 at 1:55 PM, Rajesh Raju
> <>wrote:
>> Dear Carlos,
>> Thank you very much for your reply. I have attached the receptor
>> 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
>> receptor. I can do the umbrella sampling in two different ways. One
>>way is
>> to make the coordinate and tolopoly files for different distance
>> 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
>> 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 <> 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
>>> 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
>>> 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
>>> difficult to properly sample over all other motions (such as side
>>> ligand flexibility, etc.
>>> given that, I'm not sure quite what you're asking. It seems that you
>>> different numbers of waters. you can adjust the water buffer length
>>> 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
>>> <>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
>>>> 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
>>>> the same coordinate files with center of masses of two molecules
>>>> 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
>>>> 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
>>>> _______________________________________________
>>>> AMBER mailing list
>>>> _______________________________________________
>>> AMBER mailing list
>> _______________________________________________
>> AMBER mailing list
> _______________________________________________
> AMBER mailing list

AMBER mailing list
Received on Thu Mar 10 2011 - 10:00:04 PST
Custom Search