Re: AMBER: Simulating proteins with calcium ion

From: 张勇 <clarkzhy.mail.bnu.edu.cn>
Date: Wed, 13 Dec 2006 08:25:03 +0800

Hi,
  I am performing the MD simulation about calcium-binding protein. In my
experience, the calcium parameter in parm99.dat of Amber8/9 is a little big. when
I do periodic boundary condition(PBC) simulation with TIP3P water model,the Ca-O
distance is 2.4-2.7, a little bigger than experimental value 2.2-2.6.

  but ,when I use the parameter posted by Kenley Barrett on AMBER achieve, and
reduced the radius of Ca2+ to about 1.3. the calcium ions escape
its binding site druing the MD in the C2 domain protein.

 so,I think the calcium parameter in parm99.dat is just OK for explicit water
model, periodic boundary condition(PBC) simulation, through it cause a little
bigger Ca-O distance.

在您的来信中曾经提到:
>From: Karen Callahan <graylavender.yahoo.com>
>Reply-To: amber.scripps.edu
>To: amber.scripps.edu
>Subject: Re: AMBER: Simulating proteins with calcium ion
>Date:Tue, 12 Dec 2006 11:19:49 -0800 (PST)
>
>Hi,
>
> In my limited experience, the rmin value for Ca2+ (C0)
> in the parm99.dat file is too large for use with POL3
> water, I cannot speak for other water models or
> molecules and simulations without polarizability. I
> have compared g(r)'s from simulation and x-ray
> diffraction experiments of 4M CaCl2 in POL3 water. The
> rmin needs to be slightly less than 1.55; whether 1.45
> or 1.5 is better I don't know. I think 1.3 will be too
> short, but I haven't tried it with calcium and have no
> absolute proof.
>
> The easiest thing to do is look up the OPLSAA force
> field, it is pretty good for Mg2+, so it might be good
> for Ca2+.
>
> You may also try the Charm force field for r-Ca2+.
>
> You will want to come up with some way to verify that
> whichever force field you use is giving reasonable
> results.
>
> Best regards,
> Karen Callahan
>
> --- Qing Zhang <qingzhang_nyu.yahoo.com> wrote:
>
> > Thanks for the replies of Fenghui and Tom. I did
> > further analysis including energy decompositions,
> > and its points to the van der Waals parameters for
> > Ca2+ in parm99.dat. I am giving a more detailed
> > description of the system/problem and my analysis.
> > The description will automatically answer some
> > questions by Fenghui and Tom, and I will explicitly
> > anwer the rest.
> >
> > The system:
> > A protein-protein complex with a structural Ca2+.
> > The Ca2+ ion binds to 6 oxygens from 5 residues (2
> > GLN, 2 ASP, and 1 GLY). The 6 oxygens form a binding
> > pocket like a half-sphere, and Ca2+ is located
> > nearly at the sphere center. The distances between
> > the oxygens and Ca2+ range from 2.2 to 2.5 Angstrom.
> >
> >
> > The problem:
> > Energy minimizations of the complex crystal
> > structure (using AMBER 9) cause Ca2+ to escape the
> > half-sphere by about 1.9 Angstrom to the solvent but
> > still binds to a few oxygens (Tom, there is no
> > move/penetration through other atoms). I used 400 SD
> > followed by 600 CG with igb=5 and a 3 kcal/mol (or
> > 10) restraint on the heavy atoms of the proteins and
> > Ca2+. Crystal waters are built into the system but
> > there is no explicit sovlent. A sample input file is
> > below.
> >
> --------------------------------------------------------
> > Minimization with Cartesian restraints
> > &cntrl
> > imin=1, maxcyc=1000, ntmin=1, ncyc=400,
> > scee=1.2,
> > igb=5,
> > ntb=0, cut=16.0,
> > ntpr=100,
> > ntr=1, restraint_wt=3.0, restraintmask=':1-297 &
> > !.H=',
> > ntc=2,
> > /
> >
> --------------------------------------------------------
> >
> > The analysis:
> > The first thing came to my mind is the radius of
> > Ca2+ in parm99.dat. As the 6 oxygens (type O2 and O)
> > have radii of 1.6612 (parm99.dat) and the distances
> > between Ca2+ and the oxygens range from 2.2 to 2.5,
> > the large raius for Ca2+ in parm99.dat (1.7131) will
> > cause a large van der Waals penalty and make Ca2+ to
> > be pushed out of the binding pocket. So I did energy
> > composition analysis on Ca2+ (idecomp=2 and the
> > restraint is removed to make idecomp work). The
> > initial structure with only 1 SD gives a vdw of
> > nal |vdw |eel |pol |sas
> > 290 0.000 49.029 -353.216 32.657
> > 0.000
> >
> > Minimization with 400 SD (no CG as Tom suggested it
> > might cause large jumps) leads to the same
> > dislocation of Ca2+ and gives a vdw of 6 and eel of
> > -350:
> > resid |internal |vdw |eel |pol
> > |sas
> > 290 0.000 5.994 -350.108 19.389
> > 0.000
> >
> > It indicates that Ca2+ is pushed out of the binding
> > pocket during minimization to reduce van der Waals
> > penalty.
> >
> > In order to further prove it, I reduced the radius
> > of Ca2+ to about 1.3. This is based on a post by
> > Kenley Barrett on AMBER achieve. In this post, the
> > vdw parameters for divalent ions computed based on
> > the Aqvist paper (JPC 1990,k 94: 8021) are listed:
> > http://amber.ch.ic.ac.uk/archive/200504/0376.html
> >
> > I took the vdw parameters of Ca2+ (1.3263, 0.4497)
> > from the post, replaced those (for C0) in
> > parm99.dat, and re-generated the topology file. The
> > energy decompostion on the initial structure with 1
> > SD show a vdw of only 6 (reduced from 49):
> > resid |internal |vdw |eel |pol
> > |sas
> > 290 0.000 6.452 -353.216 32.657
> > 0.000
> >
> > Then I minimized the system for 400 SD (same
> > minimization condition as the run without radius
> > modification). The Ca2+ ion stays at its crystal
> > location! The movement is only 0.13 Angstrom, and
> > the energy decomposition shows a vdw of 12 and eel
> > of -396:
> > resid |internal |vdw |eel |pol
> > |sas
> > 290 0.000 11.906 -395.934 61.374
> > 0.000
> >
> > From these observations, the instability of Ca2+
> > during the minimizations is clearly due to the vdw
> > parameters for Ca2+ in parm99.dat.
> >
> > I am not familiar with divalent vdw
> > parameterization. If someone has more insights on
> > this, please feel free to raise them.
> >
> > Thanks,
> >
> > Qing
> > ======================================
> > Qing Zhang, Ph.D.
> > Research Associate
> > Department of Molecular Biology, MB-5
> > The Scripps Research Institute
> > 10550 North Torrey Pines Road
> > La Jolla, CA 92037-1000
> > Tel: (858) 784-2333
> > Fax: (858) 784-2860
> > ebsite: http://www.qingzhang.info
> > ======================================
> >
> >
> >
> >
> >
> >
>
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Received on Wed Dec 13 2006 - 05:22:07 PST
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