AMBER Archive (2008)

Subject: Re: AMBER: Chloride anion ligands leave the protein during MD

From: Gustavo Seabra (gustavo.seabra_at_gmail.com)
Date: Fri Nov 14 2008 - 07:40:45 CST

Hi Francesco,

I'm sorry i got a bit confused with all the inputs... At which point
exactly does the Cl- ion start to drift? Is it as soon as you start
MD, or only when you add nrespa=2? (none of your inputs have this).

Gustavo.

On Thu, Nov 13, 2008 at 10:06 AM, Francesco Pietra
<chiendarret_at_gmail.com> wrote:
> Hi:
> I have carried out docking of a small protein against a large one, the
> latter generated with Modeller from an extremely similar natural
> protein and carrying chloride anion ligands. These were accounted for
> during docking, and in fact they conserved their position after
> docking. The docking region does not involve the chloride anions
> directly.
>
> With Amber 10 and pmemd, the complex was first minimized under GB conditions:
>
> &cntrl
> imin=1,
> maxcyc=3000,
> ncyc=1500,
> ntb=0,
> igb=5,
> cut=999
> /
>
>
> Then it was heated gradually to 300K and further equilibrated as follows::
>
> &cntrl
> imin=0, irest=0, ntx=1, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=2500, dt=0.001,
> ntpr=100, ntwx=100,
> tempi=100.0, temp0=150.0,
> cut=999.0, rgbmax=999.0,
> nmropt=1
> /
> &wt TYPE='TEMP0', istep1=0, istep2=2500,
> value1=100.0, value2=150.0,
> /
> &wt TYPE='END'
> /
>
> &cntrl
> imin=0, irest=0, ntx=1, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=2500, dt=0.001,
> ntpr=100, ntwx=100,
> tempi=150.0, temp0=200.0,
> cut=999.0, rgbmax=999.0,
> nmropt=1
> /
> &wt TYPE='TEMP0', istep1=0, istep2=2500,
> value1=150.0, value2=200.0,
> /
> &wt TYPE='END'
> /
>
> &cntrl
> imin=0, irest=0, ntx=1, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=2500, dt=0.001,
> ntpr=100, ntwx=100,
> tempi=200.0, temp0=250.0,
> cut=999.0, rgbmax=999.0,
> nmropt=1
> /
> &wt TYPE='TEMP0', istep1=0, istep2=2500,
> value1=200.0, value2=250.0,
> /
> &wt TYPE='END'
> /
>
> &cntrl
> imin=0, irest=0, ntx=1, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=2500, dt=0.001,
> ntpr=100, ntwx=100,
> tempi=250.0, temp0=300.0,
> cut=999.0, rgbmax=999.0,
> nmropt=1
> /
> &wt TYPE='TEMP0', istep1=0, istep2=2500,
> value1=250.0, value2=300.0,
> /
> &wt TYPE='END'
> /
>
> Then increased dt!!
>
> &cntrl
> imin=0, irest=0, ntx=1, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=3000, dt=0.002,
> ntpr=100, ntwx=100,
> tempi=290.0, temp0=300.0,
> cut=999.0, rgbmax=999.0,
> nmropt=1
> /
> &wt TYPE='TEMP0', istep1=0, istep2=600,
> value1=290.0, value2=300.0,
> /
> &wt TYPE='END'
> /
>
>
>
> As EPTOT ETOT EKTOT were very nearly constant and the whole complex
> had not suffered visible distotion, I tried MD of this huge,
> unabridged complex under GB conditions in very small chunks as
>
> Production under GB conditions
> &cntrl
> imin=0, irest=1, ntx=5, ntb=0,
> igb=5, ntc=2, ntf=2,
> ntt=3, gamma_ln=2.0,
> nstlim=3000, dt=0.002,
> ntpr=100, ntwx=100,
> tempi=300.0, temp0=300.0,
> cut=999.0, rgbmax=999.0
> /
>
>
> Starting from production 2, I added nrespa=2 (reaching the guard limit
> of 4femtosec)
>
> Surprisingly (for me) the chloride anions started to leave the
> protein, while no other distortion showed up. While at frame 0 the
> chloride anions are their positions, at frame 50(a base some 25 ps of
> trajectory) they are out of the proteins a gradually they disappear
> from the screen. Evaluating rmsd with ref frame 0, rmsd increases
> linearly with frame number, and in the attached plot. The minimum
> potential energy remains at frame 100, out of 250 frames, and ETOT
> (black), EPTOT (green), and EKTOT (red) seem OK as in the attached
> plot. Nonetheless, might the large nrespa=2 be responsible for the
> instability of chloride anion ligands? The size of the system is such
> that the 50% gain with nrespa=2 is difficult to renounce to.
>
> Chloride anion was set as Cl- and xleap did not complain about.
>
> Sorry if I made a long story for something trivial, obvious to
> experienced people.
>
> Thanks for any kind of comment
> francesco pietra
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