[gmx-users] Assembling a good simulation starting point

John Ladasky blind.watchmaker at yahoo.com
Fri Feb 19 04:08:11 CET 2010

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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