[gmx-users] references on binding

David Mobley dmobley at gmail.com
Mon Jan 16 17:25:41 CET 2006

I tried to do this initially, but it is pretty hard. Unless there is a
really good/big funnel to the active site, you essentially have the problem
of the ligand doing a random walk in 3-space (really, 6-space, I guess,
since it typically also needs to be in the right orientation to bind as
well). You can make some quick estimates of how long it will take to find
the binding site based on the volume  of  your system and the diffusion
constant, but typically I think this will be longer than you want to run MD.

My advice is to start by "cheating". First see if you can get the ligand to
bind by, say, pulling it into the binding site with some fairly weak
restraints. If you can't do this then you have absolutely no  hope of
getting it there without cheating. On the other hand, if you can, then you
can do something more sophisticated (i.e. start it *near* the binding site
and run a bunch of different trajectories, discarding the ones where it
random walks *away* from the site, and keep only the ones where it binds or
looks like it might bind). This is all if you insist on looking at
trajectories only. If I were you I would probably use umbrella sampling to
compute the PMF instead.

Best wishes,
David Mobley

On 1/15/06, Diego Vallejo <diego.vallejo at gmail.com> wrote:
> Hello,
> I would like to know about MD simulations of a protein-ligand binding
> process (not MD of complexes or  Free Energy Calculations, not steered
> dynamics, nor with pull springs, etc.)
> I mean a simulation starting from two molecules far apart and ending
> with the complex without artificial forces.
> Could you please pass the main references? (David, Erik,  Anton...?)
> Could be with gromacs or not.
> Thanks a lot.
> Diego Vallejo
> vallejo at iflysib.unlp.edu.ar
> diego.vallejo at gmail.com
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