Re: [AMBER] Umbrella sampling coordinate question

From: Rajesh Raju <>
Date: Wed, 09 Mar 2011 12:55:38 -0600

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

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
> 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
>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
> 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
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Received on Wed Mar 09 2011 - 11:00:05 PST
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