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.<br>
<br>
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.<br>
<br>
Best wishes,<br>
David Mobley<br>
UCSF<br><br><div><span class="gmail_quote">On 1/15/06, <b class="gmail_sendername">Diego Vallejo</b> <<a href="mailto:diego.vallejo@gmail.com">diego.vallejo@gmail.com</a>> wrote:</span><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
Hello,<br><br>I would like to know about MD simulations of a protein-ligand binding<br>process (not MD of complexes or Free Energy Calculations, not steered<br>dynamics, nor with pull springs, etc.)<br>I mean a simulation starting from two molecules far apart and ending
<br>with the complex without artificial forces.<br>Could you please pass the main references? (David, Erik, Anton...?)<br>Could be with gromacs or not.<br>Thanks a lot.<br><br>Diego Vallejo<br><a href="mailto:vallejo@iflysib.unlp.edu.ar">
vallejo@iflysib.unlp.edu.ar</a><br><a href="mailto:diego.vallejo@gmail.com">diego.vallejo@gmail.com</a><br>_______________________________________________<br>gmx-users mailing list<br><a href="mailto:gmx-users@gromacs.org">
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