ok sir.
I wil read more papers. Thank you very much.
mary
On Tue, Mar 22, 2016 at 11:38 PM, Ray Luo <rluo.uci.edu> wrote:
> I meant the second choice (1-10ns, 1-20ns, 1-30ns etc) is how to check
> cumulative average.
>
> If this is still confusing, I suggest you read some papers on free
> energy simulations. Convergence check is not trivial in general.
>
> 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 Tue, Mar 22, 2016 at 2:43 AM, Mary Varughese <maryvj1985.gmail.com>
> wrote:
> > Sir,
> >
> > This is a nucleic acid-ligand complex. i do single trajectory 15ns trial
> > which failed and then a multiple trj 10 ns . which also failed. in both
> > cases i do mmpbsa over a 3 ns of the trj to the max with freq 50 so that
> > 60 frames. It worked with other ligands (which were more rigid).
> >
> > did u mean, 1-10 ns, then 1-10 ns, then 1-10 so on or
> > 1-10 ns, then 1-20 ns then 1-30 so on?
> >
> > sir, you usually do mmpbsa over the whole trajectory (isnt it highly
> memory
> > intensive and time consuming?)? for both single and multiple approach?
> >
> >
> >
> > thanking you
> >
> > mary
> >
> >
> >
> >
> >
> > On Tue, Mar 22, 2016 at 11:41 AM, Ray Luo <rluo.uci.edu> wrote:
> >
> >> Mary,
> >>
> >> Very likely it is due to the lack of convergence. Assuming that your
> >> MD behaves well, i.e. not unfolding the protein etc. 10ns seems very
> >> short for multi-traj MMPBSA of typical-sized proteins.
> >>
> >> A straightforward but slow way to check convergence is to restart your
> >> MD for 10ns each time and apply MMPBSA with snapshots from each of the
> >> following sets of trajectories:
> >>
> >> 10ns, 20ns, 30ns, ... 100ns and so on.
> >>
> >> You'll get a MMPBSA average energy for each of the above sets. Plot
> >> these cumulative average energies versus the simulation times (10ns,
> >> 20ns, ..., 100ns, and so on) and you'll see whether the cumulative
> >> average is converged, i.e. not changing much any more.
> >>
> >> Of course if you have a good statistical software, you may be able to
> >> get a plot of the cumulative average over simulation time given all
> >> the snapshots at once (for example all of the 100ns).
> >>
> >> 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 Mon, Mar 21, 2016 at 7:06 PM, Mary Varughese <maryvj1985.gmail.com>
> >> wrote:
> >> > Sir,
> >> >
> >> > Infact i have tried multiple trajectory approach also (10 ns
> trajectory).
> >> > But didnt get any favorable result.
> >> >
> >> > May be because i havent considered "make sure the average
> >> > delta G has converged by checking cumulative averages of all three
> >> > runs (complex, receptor, and ligand)". Would you please explain
> >> cumulative
> >> > average?
> >> > And also about entropy estimation. ? It would be really helpful.
> >> >
> >> > Thanking you for your time and reply
> >> >
> >> > mary
> >> >
> >> >
> >> > On Tue, Mar 22, 2016 at 6:09 AM, Ray Luo <rluo.uci.edu> wrote:
> >> >
> >> >> 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 Tue Mar 22 2016 - 16:30:04 PDT
