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-- 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 >> >> >> > _______________________________________________ >> >> >> > AMBER mailing list >> >> >> > AMBER.ambermd.org >> >> >> > http://lists.ambermd.org/mailman/listinfo/amber >> >> >> > >> >> >> _______________________________________________ >> >> >> AMBER mailing list >> >> >> AMBER.ambermd.org >> >> >> http://lists.ambermd.org/mailman/listinfo/amber >> >> >> >> >> > >> >> > _______________________________________________ >> >> > AMBER mailing list >> >> > AMBER.ambermd.org >> >> > http://lists.ambermd.org/mailman/listinfo/amber >> >> > >> >> >> >> _______________________________________________ >> >> AMBER mailing list >> >> AMBER.ambermd.org >> >> http://lists.ambermd.org/mailman/listinfo/amber >> >> >> > _______________________________________________ >> > AMBER mailing list >> > AMBER.ambermd.org >> > http://lists.ambermd.org/mailman/listinfo/amber >> >> _______________________________________________ >> AMBER mailing list >> AMBER.ambermd.org >> http://lists.ambermd.org/mailman/listinfo/amber >> > _______________________________________________ > AMBER mailing list > AMBER.ambermd.org > http://lists.ambermd.org/mailman/listinfo/amber _______________________________________________ AMBER mailing list AMBER.ambermd.org http://lists.ambermd.org/mailman/listinfo/amberReceived on Tue Mar 22 2016 - 11:30:04 PDT