Re: [AMBER] MMPBSA doubt

From: Ray Luo <rluo.uci.edu>
Date: Mon, 21 Mar 2016 17:39:19 -0700

Hi Mary,

If you have a flexible ligand, the single trajectory approach is
probably not the best way to go. Please try the multi-trajectory
approach. Apparently, a key point here is to make sure the average
delta G has converged by checking cumulative averages of all three
runs (complex, receptor, and ligand). However, some sort of entropy
estimation is also important to take into account the conformational
flexibility in the delta G calculation.

All the best,
Ray

--
Ray Luo, Ph.D.
Professor
Biochemistry, Molecular Biophysics, Chemical Physics,
Chemical and Biomedical Engineering
University of California, Irvine, CA 92697-3900
On Fri, Mar 18, 2016 at 9:48 PM, Mary Varughese <maryvj1985.gmail.com> wrote:
> sir,
>
> these are the files used to calculate PBTOT and entropy. I have done it
> with other ligands(more rigid ligands) successfully. The problem here is
> that the current ligand is half part flexible(a  ch2-ch2-ch2-ch3 flexible
> chain). Though the ligand bind experimentally and theoretically(throughout
> the simulation time) the movement of the flexible region is causing changes
> in PBTOT and entropy such that i cant get a statistically reliable value
> (the final value obtained are highly positive; when i check the values (BE)
> for each frame its deviating very much). The flexible part is causing that.
>
> So i would like to know which strategy i should be adopted in such cases.
>
>
> thanking you for ur reply
>
> On Sat, Mar 19, 2016 at 6:43 AM, Ray Luo <rluo.uci.edu> wrote:
>
>> Mary,
>>
>> Maybe a bit more info is helpful, i.e. your inpu file. Also please note
>> that mmpbsa single trajectory approach is more useful for delta delta G
>> estimation.
>>
>> All the best,
>> Ray
>> On Mar 16, 2016 5:20 PM, "Mary Varughese" <maryvj1985.gmail.com> wrote:
>>
>> > Sir,
>> >
>> > I run some DNA-ligand1 complexes. Though the ligand remains bind
>> throughout
>> > the simulation, (the ligand binds experimentally also), I am not getting
>> a
>> > favorable binding energy from MMPBSA (single trajectory approach). The
>> > ligand has a CH2-CH2-CH2 chain on one end which causes the ligand some
>> > movement (entropy changes) and hence a stable binding energy is not
>> > possible. Is there any other way to quantify the binding energy. Would
>> you
>> > please suggest a reliable approach in such situations where the ligand
>> has
>> > much flexibility?
>> >
>> > thanking you
>> > mary
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Received on Mon Mar 21 2016 - 18:00:03 PDT