this sounds like there are many reasons why your simulation could be
unstable and not just because of using the cap.
making mutations to a homology model and expecting ligands to bind well in
MD is a very challenging project that would take significant expertise and
experience. I think you need to look carefully at each step of your protocol
(all the way from the start) and determine a way to test how reliable it is
(find a control). you can't just assume it's the cap that causes trouble-
unless you show that the same system works just fine with normal solvation.
On Mon, May 3, 2010 at 8:49 PM, Rilei Yu <yulaomao1983.yahoo.com.cn> wrote:
> Hi,
>
> Thanks for your reply! Here is my answer to your question:
> you haven't given enough information- how did you generate the initial
> structure?
> Here, I created the structure based on homology modeling. In fact it is a
> refined complex, from 10 ns MD (very stable for the wide type). When I
> obtained, this complex, I did a series of mutations on the complex . Then I
> try to use solvatecap to do 500 ps MD to refine every complexes (mutants).
>
> how did you do the equilibration?
>
> Firstly, I minimize the water, then minimize the whole system;
> Secondly, I used 20 ps increase T from 0 to 300; then equilibrate it using
> 30 ps.
> Thirdly, it is the production stage attached below.
>
> are all of the force field parameters standard, or did you create any new
> ones?
>
> I think it should be standard, as I obtained these parameter based the
> tutorial. But I am still not so confident.
>
> what are you restraining?
> I restrain residues (of the receptor) outside the binding site (with a
> radius of 6).
>
> Can you give me more suggestions? I found using solvatecap can really
> amazing some time, but also sometime it makes the system change too
> drastical. I can hardly believe it.
>
> Best regards,
> Rilei Yu
>
> --- 10年5月4日，周二, Carlos Simmerling <carlos.simmerling.gmail.com> 写道：
>
> 发件人: Carlos Simmerling <carlos.simmerling.gmail.com>
> 主题: Re: [AMBER] molecular dynamics set up
> 收件人: "AMBER Mailing List" <amber.ambermd.org>
> 日期: 2010年5月4日,周二,上午7:57
>
> you haven't given enough information- how did you generate the initial
> structure? how did you do the equilibration? are all of the force field
> parameters standard, or did you create any new ones? what are you
> restraining?
>
> >
> >
> >
> > Dear AMBER users,
> >
> > Recently, I tried to using solvatecap to simulate my system for faster
> > speed. Unfortunately, sometime the ligands change drastically, even the
> > ligand goes out the binding site in some simulation.
> >
> > I try to solve this problem using all kinds of ways:
> > extending the cap radius;
> > using smaller steps(0.001);
> > adding some restraint;
> > slowly increasing T;
> > Unfortunately, the system is still not very stable as I expected. Here, I
> > give the simulation file as follows and really hope anyone can give me
> some
> > suggestions:
> > #ntx=5,
> > irest=1,
> > imin=0,
> > ntpr=1000,
> > ntwx=1000,
> > ntwr=5000,
> > nstlim=250000,
> > dt=0.001,
> > ntt=3,
> > gamma_ln = 1.0,
> > temp0=300,
> > tempi=300,
> > tautp=1,
> > igb=0,
> > ntb=0,
> >
> > ntf=2,
> > ntc=2,
> > cut=15,
> > ntr=1,
> > fcap=2.5,
> > ivcap=0,
> > tol=0.000001,
> > ntr=1, restraint_wt=5.0, restraintmask=':1-92, 95-144, 153-185,
> 200-243,
> > 251-266, 273-288, 292-320, 324-326, 332-372, 375-377, 382-419',
> > #I am really appreciated for your help!
> >
> > Rilei Yu
> >
> >
> >
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> >
> >
> >
> >
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> >
> >
> >
> >
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> >
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Received on Tue May 04 2010 - 06:30:03 PDT
