yes, you should use the number of atoms without water. keep in mind that
this is a simple guide, and these calculations will be approximate in the
best case.
On Wed, Apr 3, 2024 at 9:06 PM Yang Wei via AMBER <amber.ambermd.org> wrote:
> Dear Professor,
>
> Thank you for your suggestions.
>
> I have implemented the autoimage command for the RMSD analysis of the
> complex, and now the RMSD of each frame is less than 5.
>
> Another question is that, when considering the number of frames for the
> entropy analysis, which should be at least three times the number of atoms
> in the complex system, should I also include the number of atoms from
> explicit water? I'm confused because ultimately, in MM-PBSA analysis, all
> explicit water and contour ions are removed during post-processing.
>
> On Mon, Apr 1, 2024 at 12:35 PM Carlos Simmerling <
> carlos.simmerling.gmail.com> wrote:
>
> > in MM-PBSA analysis, you are removing all of the explicit water during
> the
> > postprocessing. So as long as the original simulations were reasonable,
> > there is no need to try to match up the exact # water molecules or even
> the
> > solvate command cutoff distance.
> > if the numerical values that you listed (2 columns) are the rmsd values,
> I
> > suspect this is an imaging issue. In your periodic system, molecules get
> > "wrapped" in the periodic box, but you want to put them back together
> > before calculating rmsd of a complex. Try using the cpptraj autoimage
> > command prior to the rms command.
> >
> > On Mon, Apr 1, 2024 at 11:36 AM Yang Wei via AMBER <amber.ambermd.org>
> > wrote:
> >
> >> Dear AMBER Community,
> >>
> >> I am currently employing MMPBSA with a multiple trajectory approach to
> >> compute the binding free energy of two systems. The first involves the
> >> interaction between a protein (123 amino acids/2,047 atoms) and a single
> >> molecule (132 atoms), while the second entails a protein-protein complex
> >> (123 amino acids/2,047 atoms and 163 amino acids/2,765 atoms,
> >> respectively).
> >>
> >> 1. For the 1st system, 10 angstrom is used for the solvatebox of the
> >> complex (protein-molecule), so that 8,938 water (or 26,814 atoms) was
> >> added. The input for the MD simulation is written as follows:
> >>
> >> NVT production 200 ns
> >> &cntrl
> >> imin=0, irest=0,
> >> nstlim=200000000, dt=0.002, ntx=1,
> >> ntpr=1000, ntwx=1000, ntwr=50000,
> >> cut=12, ntb=1,
> >> ntc=2, ntf=2,
> >> ntt=3, gamma_ln=2.0,
> >> tempi=300.0, temp0=300.0,
> >> ioutfm=1, ntwv=-1, ig=-1, iwrap=1
> >> &end
> >> &wt
> >> type='END'
> >> &end
> >>
> >> Currently, I have maintained an equal number of water molecules for the
> >> complex (protein-molecule), receptor (protein), and ligand (molecule) to
> >> preserve concentration. However, utilizing 8,938 water molecules for
> >> ligand
> >> (a single molecule) appears excessive and computationally wasteful. I
> did
> >> a
> >> test by employing 3000 water molecules for ligands and the resulting
> >> binding energy difference is only around ~1 kcal/mol. My question is
> that
> >> whether it is necessary to employ the same number of water molecules for
> >> all components, and if the implicit model necessitates an equivalent box
> >> size as the explicit model.
> >>
> >> 2. For the second system, a 10 angstrom solvate box was employed for the
> >> protein-protein complex, resulting in the addition of 19,629 water
> >> molecules (or 58,887 atoms). Apart from nstlim=400000000, the input for
> >> the
> >> MD simulation remains identical to the first system.
> >>
> >> Prior to the MMPBSA analysis, an RMSD analysis was conducted:
> >>
> >> parm ../../Ternary_VHL_solv.prmtop
> >> trajin ../../Ternary_VHL_solv_nvt_prod.netcdf
> >> reference ../../Ternary_VHL_solv.inpcrd
> >>
> >> rms :1-285.N,CA,C reference out rmsd.agr
> >>
> >> quit
> >>
> >> Upon visualizing the frames (e.g., Frame 92253 and Frame 92254), the
> >> fluctuations were likely caused by the size of the box.
> >> .....
> >> 92251.000 2.9623
> >> 92252.000 3.0159
> >> 92253.000 2.9695
> >> 92254.000 31.2806
> >> 92255.000 31.2697
> >> 92256.000 31.3480
> >> 92257.000 31.2952
> >> 92258.000 31.3905
> >> 92259.000 31.4305
> >> 92260.000 3.0645
> >> 92261.000 3.0589
> >> 92262.000 3.0633
> >> .....
> >>
> >> I'm concerned about the potential impact of these fluctuations on the
> >> MMPBSA analysis and whether enlarging the size of the water box would be
> >> necessary. This could lead to longer simulation times and require more
> >> frames for the entropy analysis.
> >>
> >> Thank you in advance.
> >>
> >> Best,
> >>
> >> Yang
> >> _______________________________________________
> >> AMBER mailing list
> >> AMBER.ambermd.org
> >> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> >
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Received on Thu Apr 04 2024 - 07:00:02 PDT
