are you trying to calculate teh absolute binding free energy? there is lots
of work on this in the literature that you should read, it can be much more
difficult than relative affinities.
On Thu, Mar 10, 2011 at 12:45 PM, Rajesh Raju <
rajesh.raju.mail.chem.tamu.edu> wrote:
> 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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> >>
> >>
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Received on Thu Mar 10 2011 - 10:00:06 PST
