Dear Shulin,
There are a number of things that could potentially cause what you are
seeing. One is the initial position of the ligand. How was this determined?
Is there is a crystal structure for it or did somebody dock it in place? If
it the latter case then the position may be off and so the ligand would
rapidly change orientation and move away from the peptide. Take a close look
at any close contacts between the protein and the ligand perhaps it is too
close. Especially when it was protonated. You may need to minimise the
protons first and then heat slowly etc.
Secondly take a look at any potential hydrogen bonds between the ligand and
the protein. In you initial structure are things orientated correctly for
these bonds? Be particularly aware of the placement of hydrogens they are
not necessarily in the optimum position and could take a very long time to
equilibrate... There are some programs around that will try to optimise
these positions for you but I forget what they are called. If you have a
small enough number though you may try to position the important hydrogens
yourself.
Thirdly there may be problems with the parameters for the ligand. How did
you obtain parameters and charges for the ligand? If you used AM1-BCC for
the charges try using a full abinitio / resp approach. Also carefully look
at the ligand atom types etc, do they all make sense.
Finally, is the ligand known to be stable in the binding site? It may be
that in reality it doesn't bind and what you are seeing is correct...
All the best
Ross
/\
\/
|\oss Walker
| Department of Molecular Biology TPC15 |
| The Scripps Research Institute |
| Tel:- +1 858 784 8889 | EMail:- ross.rosswalker.co.uk |
|
http://www.rosswalker.co.uk/ | PGP Key available on request |
Note: Electronic Mail is not secure, has no guarantee of delivery, may not
be read every day, and should not be used for urgent or sensitive issues.
> -----Original Message-----
> From: owner-amber.scripps.edu
> [mailto:owner-amber.scripps.edu] On Behalf Of Shulin Zhuang
> Sent: 29 June 2005 03:12
> To: amber.scripps.edu
> Subject: Re: AMBER: Is the MD simulation normal
>
> Dear Prof. Duan and Prof. Ross,
>
> Another important figure is attached.
>
> I samples several snapshots from the NPT trajectory and superimpose
> them. The ligand slide much away from the initial position.
> Superimposition of the complex reveals that the RMSD of the protein is
> relatively small, 0.8 or so. Indeed , the backbone RMSD of the
> protein along the whole trajectory is under 1.0 angstrom.
>
> I spent one month or so to this problem and still not work it out .
>
> Best regards
>
> --
> Shulin Zhuang
> Chemistry Department
> Zhejiang University PRC
> shulin.zhuang.gmail.com
>
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber.scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
Received on Wed Jun 29 2005 - 17:53:00 PDT
