[gmx-users] Assembling a good simulation starting point

Dallas B. Warren Dallas.Warren at pharm.monash.edu.au
Fri Feb 19 07:07:36 CET 2010

Can you run that same procedure without doing anything to your protein?


Catch ya,

Dr. Dallas Warren
Drug Delivery, Disposition and Dynamics
Monash Institute of Pharmaceutical Sciences, Monash University
381 Royal Parade, Parkville VIC 3010
dallas.warren at pharm.monash.edu.au
+61 3 9903 9167
When the only tool you own is a hammer, every problem begins to resemble
a nail. 


From: gmx-users-bounces at gromacs.org
[mailto:gmx-users-bounces at gromacs.org] On Behalf Of John Ladasky
Sent: Friday, 19 February 2010 2:08 PM
To: gmx-users at gromacs.org
Subject: [gmx-users] Assembling a good simulation starting point


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


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