AMBER Archive (2006)

Subject: Re: AMBER: Simulating proteins with calcium ion

From: Karen Callahan (graylavender_at_yahoo.com)
Date: Tue Dec 12 2006 - 13:19:49 CST

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_at_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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