[gmx-users] Simulation with ligand on protein surface

adam zalewski adam.zalewski at mail.com
Sat Jul 11 08:51:19 CEST 2015

Hi Justin and sorry for the vagueness

What I'm observing are displacements from the binding site (granted, 
they are quite shallow) and loss of any relation to the experimental 
data. They also happen fairly fast (often below 10ns) and just looking 
at the trajectory, makes me think something is wrong (e.g. a nicely 
buried phenyl ring being exposed into the solvent). Now that you mention 
it, the ligand parametrization does seem like the place to look. Any 
hints regarding that (acpype/antechamber or otherwise) ?

Thanks and a nice weekend,

On 07/10/2015 11:09 PM, Justin Lemkul wrote:
> On 7/10/15 5:02 AM, az wrote:
>> Hi all
>> I was wondering if anyone had experience/pointers regarding simulating
>> protein-ligand systems where the interface was heavily surface-exposed ?
>> I've been running quite a few of those these days with 
>> Amber99SB--ildn, TIP3P,
>> and acpype (i.e. Ambertools) for ligand parametrization, mainly for 
>> the purpose
>> of probing stability of peptidomimetic docking poses (10-50ns; aside 
>> from the
>> force-field I follow Justin Lemkul's tutorial quite closely). Having 
>> however
>> noticed that some of my reference ligands (i.e. ones with 
>> crystallographic/NMR
>> data) wander away from where they should remain, I started wondering 
>> whether
>> there could be something wrong with my setup. I obviously understand 
>> there's a
>> zillion possibilities here, but I was still wondering whether there 
>> exists some
>> sort of 'good-practice' for such cases (e.g. choice of force-fields,
>> equilibration protocols ... anything really). I cannot be the only 
>> one doing
>> this and if anyone has a protocol that served them well in the past, 
>> I'd love to
>> learn about it.
> In general, if an interaction is not preserved, that suggests a poor 
> parametrization of that ligand.  But "wander away" is a bit vague; if 
> it's just a small reorientation or something, it may not actually be 
> "wrong" at all. Depends on the quality of the experimental data and 
> the agreement with experimental conditions, as well.
> -Justin

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