Very thanks for your reply again! I will make a control by simulating the same system using while box way. In that case, it should be easier to find the problem.
By the way, can we use PME to simulate the cap system? It seemed that I could not.
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,下午9:07
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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Received on Tue May 04 2010 - 17:30:03 PDT
