Hi, Jason
Thanks for your comment.
It's very useful.
Best regards,
Biao MA
On Thu, Jul 4, 2013 at 11:20 PM, Jason Swails <jason.swails.gmail.com>wrote:
> On Wed, Jul 3, 2013 at 8:47 PM, Biao Ma <jackyma1981.gmail.com> wrote:
>
> > Hello, amber users,
> >
> > Now, I am reading a paper that is "Insights into structural properties of
> > denatured human prion 121-230 at melting temperature studied by replica
> > exchange molecular dynamics". Base on the describe of paper, I write the
> > process and the input file of amber simulation, but I cannot sure that is
> > correct.****
> >
> > Who can help me check it?****
> >
>
> I'll offer some help and comments, but on the whole there is too much here
> to offer an in-depth evaluation of your procedure in a reasonable amount of
> time. In general, the best way to validate a specific scheme is to try it
> on some systems, especially ones where you already know what the answer
> should be.
>
>
> > **
> > Thank a lot.
> > Biao Ma
> > **
> > pumed url of the paper: http://www.ncbi.nlm.nih.gov/pubmed/22339436****
> >
> > ** **
> >
> > Blow is a part of method in the paper:****
> >
> > =====start
> > In this work, the temperature setting used for sheep PrP 125-230 such
> that
> > MD simulations were exchanged at 320.0, 322.0,324.0, 326.0, 328.1, 330.2,
> > 332.3, 334.4, 336.5, 338.6, 340.8, 343.0, 345.2, 347.4, 349.6, 351.8,
> > 354.0, 356.2, 358.5, 360.8, 363.1, 365.4, 367.7, and 370.0 K was used.
> All
> >
>
> These temperatures appear to be evenly spaced. I would suggest using a
> geometric temperature series to optimize the performance of replica
> exchange. I have found this server [http://folding.bmc.uu.se/remd/] to be
> remarkably accurate.
>
>
> > of the replicas were equilibrated for 20 ns without exchanging
> temperatures
> > and then extended for 65 ns of REMD simulation. The generalized Born
> model
> > used in this study modified the calculation of Born radii and improved
> the
> > accuracy in the solvent polarization for macromolecules. The
> combinational
> > use of the all-atom point-charge force-field (also known as ff03) and the
> > generalized Born model led to successful folding of several proteins. The
> > AMBER 11 simulation package 26 was used in both REMD simulation and data
> > analysis. The melted huPrP 121-230 was computed starting from an extended
> > huPrP. To generate the initial extended structure, a heating method was
> > applied to a known NMR structure (PDBcode 1hjn,15Figure 1A), enabling it
> to
> > unfold at 600 K for 40 ns of MD simulation to result in an extended
> > conformation (Figure 1B) as described previously.****
> >
> > During this simulation, the disulfide covalent bond between residues 179
> > and 214 was preserved. In total, 24 replicas with duration of 65 ns and
> > with an integration time step of 2 fs were computed based on the extended
> > huPrP with different random number seeds to generate the initial
> > conditions. A 16 Å force-shifted non-bonded cutoff and generalized Born
> > solvent models with salt concentration of 0.2 M were applied.****
> >
> > **=====end
> > **
> >
> > **
> >
> > **
> >
> > Simulation Procedure:****
> >
> > 1. system building****
> >
> > 2. system minimization****
> >
> > 3. heating system****
> >
> > 4. generate the extend conformation****
> >
> > 5. local minimization after heating system****
> >
> > 6. equilibrate the every replica****
> >
> > 7. REMD simulation****
> >
> > ** **
> >
> > ** **
> >
> > *1.leap.inp for system building*
> >
> > ** **
> >
> > source pdb: 1ag2****
> >
> > use the the ff03 (Duan et al.) force field****
> >
> > ** **
> >
> > leap.inp
> >
> > source leaprc.ff03.r1****
> >
> > set default PBradii mbondi2****
> >
> > # load pdb file****
> >
> > 1ag2 = loadPdb input.pdb****
> >
> > savePdb 1ag2 1ag2.pdb****
> >
> > bond 1ag2.179.SG <http://1ag2.179.sg/> 1ag2.214.SG <http://1ag2.214.sg/
> > >****
> >
> > # save 1ag2 to prmtop and inpcrd files****
> >
> > saveAmberParm 1ag2 1ag2.prmtop 1ag2.inpcrd****
> >
> > # finish****
> >
> > quit****
> >
> > ** **
> >
> > 2. system minimization****
> >
> > minimisation for heated system****
> >
> > &cntrl****
> >
> > imin=1, maxcyc=1000, ncyc=500,****
> >
> > igb=5, ntb=0,****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
>
> This cutoff is too small IMO. I've seen people use a cutoff of 30 Å when
> employing a salt concentration like the one you have, but I would suggest
> using an infinite cutoff with a GB simulation.
>
>
> >
> > ntpr=100****
> >
> > /****
> >
> > ~****
> >
> > ~****
> >
> > ** **
> >
> > *3. heat the system*
> >
> > heating system from 0 K to 600K during 100 ps.****
> >
> > &cntrl****
> >
> > nstlim = 50000, dt = 0.002,****
> >
>
> At 600 K, a 2 fs time step may be too short.
>
>
> > ntt = 1, tautp = 1.0,****
> >
>
> I would suggest using Langevin dynamics to maintain your temperature,
> since it is more theoretically rigorous than the Berendsen thermostat.
>
> ntt = 3, gamma_ln=1.0, ig=-1,
>
>
> > tempi = 0, temp0 = 600, ntc =2, ntf = 2,****
> >
> > ntpr =100, ntwx = 100,****
> >
> > ntb = 0, igb = 5, ****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
> > nmropt = 1,****
> >
> > /****
> >
> > &wt****
> >
> > type = 'TEMP0', istep1 = 0, istep2 =50000, value1 = 0, value2=600,****
> >
> > /****
> >
> > &wt type = 'END'****
> >
> > /****
> >
> > ** **
> >
> > *4**. **generate the full unfolded conformation*
> >
> > ** **
> >
> > To generate the initial extend structure, a heating method was used to a
> > known NMR structure (PDB code:1ag2), enabling it to unfold at 600 K for
> 40
> > ns of LD simulation to result in an extended conformation.****
> >
> > here, I do not sure whether I do the restart MD(set irest = 1, ntx = 5,
> or
> > irest = 0, ntx = 1), Simulation results is difference, which setting
> should
> > I use?
> >
>
> Since the last simulation ended at 600 K, you should just restart. The
> results will actually be different between any two runs (generally, unless
> you run 2 identical sets of inputs on the same model GPU).
>
>
> >
> > 40nsld.inp****
> >
> > enabling the heated NMR structure to unfold at 600 K for 40ns of LD
> > simulation****
> >
> > &cntrl****
> >
> > irest = 1, ntx = 5,****
> >
> > nstlim = 20000000, dt = 0.002,****
> >
> > ntt = 3, gamma_ln = 1.0,****
> >
>
> Make sure you set an explicit value for ig (the random number seed). It
> should be different for every simulation or you will begin to see
> synchronization artifacts. http://pubs.acs.org/doi/abs/10.1021/ct800573m
>
> Setting ig=-1 will pull the random seed from the wall clock, ensuring that
> they are different for each run.
>
>
> >
> > tempi = 600,temp0 = 600,****
> >
> > ntb = 0, igb = 5,****
> >
> > ntpr = 500, ntwx = 1000, ntwr = 2000000,****
> >
> > ntc = 2, ntf = 2,****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
> > /
> >
> >
> > 600kmd.inp****
> >
> > enabling the heated NMR structure to unfold at 600 K for 40ns of LD
> > simulation****
> >
> > &cntrl****
> >
> > irest = 0, ntx = 1,****
> >
> > nstlim = 20000000, dt = 0.002,****
> >
> > ntt = 3, gamma_ln = 1.0,****
> >
> > tempi = 600,temp0 = 600,****
> >
> > ntb = 0, igb = 2,****
> >
> > ntpr = 500, ntwx = 1000, ntwr = 2000000,****
> >
> > ntc = 2, ntf = 2,****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
> > /
> >
> > 40nsld.out irest = 1, ntx = 5,****
> >
> > 600kmd.out irest = 0, ntx = 1****
> >
> > [image: 40nsld.etot.png]****
> >
> > [image: 600kmd.etot.png]
> >
> >
> > ** **
> >
> > 5. local minimization after heating system****
> >
> > use the mdin file which is same to step 3 above。****
> >
> > ** **
> >
> > 6. equilibrate the every replica****
> >
> > ** **
> >
> > equilibrate.mdin****
> >
> > ** **
> >
> > equilibration 20 ns, every 10ps save output. <- Is this must to do
> > equilibrate for 20 ns?**
> >
> > equilibration****
> >
> > &cntrl****
> >
> > irest=0, ntx=1,****
> >
> > nstlim=10000000, dt=0.002,****
> >
> > irest=0, ntt=3, gamma_ln=1.0,****
> >
> > temp0=XXXXX, ig=RANDOM_NUMBER,****
> >
>
> You can just use ig=-1.
>
>
> >
> > ntc=2, ntf=2, nscm=1000,****
> >
> > ntb=0, igb=5,****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
> > ntpr=5000, ntwx=5000, ntwr=10000000,****
> >
> > nmropt=1,****
> >
> > /****
> >
> > &wt TYPE='END'****
> >
> > /****
> >
> > DISANG=system_chir.dat****
> >
> > ** **
> >
> > 7. REMD simulation****
> >
> > remd 65ns exchange every 2ps <- Here I have been confused, how often to
> > exchange is more appropriate ?****
> >
>
> For T-REMD, you don't lose any efficiency by attempting exchanges more
> often. I would attempt exchanges at least every 100 steps, although we've
> shown that convergence gets better for even more rapid exchange attempts.
>
>
> >
> > ** **
> >
> > remd.mdin****
> >
> > remd 65ns exchange every 2ps****
> >
> > &cntrl****
> >
> > irest=0, ntx=1,****
> >
> > nstlim=1000, dt=0.002,****
> >
> > irest=0, ntt=3, gamma_ln=1.0,****
> >
> > temp0=XXXXX, ig=RANDOM_NUMBER,****
> >
> > ntc=2, ntf=2, nscm=1000,****
> >
> > ntb=0, igb=5,****
> >
> > cut = 16, rgbmax = 16, saltcon = 0.2,****
> >
> > ntpr=100, ntwx=1000, ntwr=100000,****
> >
> > nmropt=1,****
> >
> > numexchg=32500,****
> >
> > /
> >
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Candidate
> 352-392-4032
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Received on Fri Jul 05 2013 - 01:00:03 PDT
