Hello John,
How large was the force after EM? Large forces often results in systems that
explode during the simulation. Also, did you minimise with or without
solvent? You assessment seems correct - the initial structure wasn't
minimised and the tools of the trade are trying different conformations,
minimising in vacuo at first and using other modelling tools before Gromacs.
Also, read a bit in the mailing list and search the literature for similar
studies.
Good luck,
Ran
On Thu, 18 Feb 2010 19:08:11 -0800 (PST)
John Ladasky <blind.watchma...@yahoo.com> wrote:
Hello everyone,
I'm a fairly new GROMACS user. I'm running GROMACS 4.0.5 on top of Ubuntu
Linux 9.10. I am still learning a lot.
I just tried to set up my first fairly complex simulation, and it failed.
I have a protein of interest, a beta barrel with a hydrophobic,
ligand-binding interior. I am interested in making mutations to this
protein, with the goal of getting it to bind to a rather different ligand
than the one it normally binds.
The way that I propose to go about studying this problem is to construct a
partially-unfolded version of the protein structure, add my ligand of
interest, and then run an energy minimization.
My first naive attempt to construct the partially-unfolded protein was not
successful. I knew that it might have problems, but I tried it anyway.
Using Biopython, I rotated the atomic coordinates so that the beta barrel
was parallel to an axis. Then I simply pulled all of the atoms 3 Angstroms
away from the axis. Finally, I inserted my ligand. Visually, inspecting
the starting structure with PyMol, I didn't see anything egregious.
However, I could have some unwanted close contacts.
I got a few "long bond" warnings from pdb2gmx, but I persisted. I got
through genbox, editconf, and my first grompp sucessfully. But then when I
tried the first, position-restrained energy minimization, it aborted with
too many LINCS warnings. I blew the system up.
These LINCS warnings could come from close contacts, or from large forces
in over-stretched bonds which resulted from my crude approach to expanding
the protein structure. Whatever the cause, I need a smarter way to start.
I am open to ANY suggestions!
What I THINK I might want to do is to manipulate the starting structure in
a more natural way. For example, selecting some peptide bonds in the beta
turns, and changing their angles. A program which allows me to manipulate
structures, and not just simulate natural forces, is what I think I need.
Surely, people who have used GROMACS will have faced problems simliar to
mine. Thanks for your advice!
John Ladasky
------------------------------------------------------
Ran Friedman
Postdoctoral Fellow
Computational Structural Biology Group (A. Caflisch)
Institute of Biochemistry
University of Zurich
Winterthurerstrasse 190
CH-8057 Zurich, Switzerland
Tel. +41-44-6355559
Skype: ran.friedman
------------------------------------------------------
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