Re: Setting up aMD simulation of a membrane protein

From: Yi Wang (yiwang198_at_gmail.com)
Date: Fri Apr 01 2011 - 13:59:01 CDT

Hi Raul,

        Your questions are really interesting, although at this point I'm not aware of any aMD studies on protein+membrane systems yet. One complexity is indeed that you can't separate the boost to the lipids and the protein, at least not in the current implementation. My suggestion would be to start from the dihedral mode, and gradually add the boost to the (total-dihedral) potential, i.e., experiment with the dual boost mode.

        The other thing I would add is that you might want to be a bit careful with the choice of 'alpha' when you boost the dihedral potential for lipids like POPC. I've been working on aMD simulations of some lipid bilayers and noticed that if alpha is set to too small a value, the cis- conformation of the double bond in the unsaturated chain of POPC may switch to a trans- conformation, which is something that you most likely don't want. All these simulations are boosting the dihedral only, and everything is done in the C27r CHARMM force field before we had the access to the latest C36 lipid force field in CHARMM. So far, the best parameter set I've experimented for POPC is E=Vavg+40*n and alpha=20*n, where n is the number of POPC molecules in the system, Vavg is the average dihedral potential of the bilayer in a short (1ns) cMD simulation (All numbers are in the kcal/mol unit).

Hope this helps & Best regards,
Yi

==================================
Yi Wang, phD
McCammon group
Department of Chemistry and Biochemistry,
University of California, San Diego
==================================

Dear NAMD users:

I'm interested in using the aMD module of NAMD 2.8b1 for the study of
possible conformational changes of a large trans-membrane protein. I
want to know how must I confront this problem in terms of defining the
aMD parameters.

1) Should I use the aMDd option, where only the dihedral angles
present on the system will be boosted?? In that case, I must have in
mind that the Lipid molecules in which the protein is embedded (POPC)
also posses dihedrals, so the will be boosted as well as the protein.
What could this produce? Should I worry about that? should I apply
constraints to the carbon atoms of the lipids to prevent a not-normal
behavior of the bi-layer? Or the value for the boosting factor should
only consider the dihedral energy of the protein atoms and with that I
will not see any exaggerated effect on the lipids?

2) On the other hand...maybe I should consider a boosting of the total system??

Any help will be most appreciated....

Raúl Araya Secchi
B.Sc Molecular Biotechnology.
Molecular Biotechnology Engineer.
PhD Student (Biotechnology Program. UNAB, Chile)
Computational Biology Lab (DLab)
Center for Mathematical Modeling (CMM)
Facultad de Ciencias Físicas y Matemáticas.
Universidad de Chile.

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