AMBER Archive (2009)

Subject: Re: [AMBER] RE: Tutorial 5

From: George Tzotzos (gtzotzos_at_mac.com)
Date: Fri Jan 16 2009 - 14:31:11 CST

Thanks Ross,

It makes perfect sense. Have a good weekend

George

On Jan 16, 2009, at 6:10 PM, Ross Walker wrote:

> Hi George,
>
> I am copying this message to the amber mailing list since it is the
> sort of
> thing that would interest other amber users as well - see
> http://lists.ambermd.org/ for signup details.
>
>> With reference to Tutorial 5
>> (http://www.rosswalker.co.uk/tutorials/amber_workshop/Tutorial_five/create
>> _prmtop.htm), I have the following query.
>>
>> If one follows the procedure you describe for the preparation of the
>> ligand, the ligand.prepin file contains the internal coordinates.
>> If one
>> were to run an md simulation with a given protein in order to
>> calculate
>> binding energies and H-bond formation, one would be dealing with two
>> different coordinate systems, namely the ligand internal
>> coordinates and
>> the protein pdb coordinates. I can't see how to run this type of
>> simulation, unless the starting ligand.pdb coordinate file was
>> originally
>> taken from a protein/ligand pdb coordinate file.
>>
>> Am I right in this assumption?
>
> Technically yes but that assumes you don't have some kind of pdb
> file with
> the coordinates in in the first place. The internal coordinates in
> the prep
> or mol2 file are only used if atoms are missing from the actual pdb
> that is
> loaded into leap, otherwise the coordinates in the pdb file are
> used. So
> indeed as you suggest you do need input structures containing
> compatible
> coordinates.
>
> Running the ligand simulation and the protein simulation separately
> with
> different coordinate sets doesn't matter, it is the simulation of the
> complex where it presents a problem. In an ideal world you would
> just place
> these two systems in solution near each other and run for an
> infinite time
> and they would explore all the phase space including all of the
> places where
> the ligand can bind and you would get perfectly weighted statistics.
> Of
> course this is not possible and thus you need to provide a structure
> which
> has the ligand coordinated to the protein in some way. The easiest
> method is
> generally to find a crystal structure that contains the ligand.
> However, if
> this is not possible then you can find something similar and
> manually place
> the ligand in the correct binding pocket - any missing atoms get
> added by
> leap based on the internal coordinates in the mol2/prep file.
>
> Alternatively if you don't have information about where the ligand
> binds
> then you would need to run some kind of docking simulation to generate
> potential structures for the protein-ligand complex - for example
> something
> like Dock. The pdb from this you would then use with leap (having
> loaded the
> relevant force field files and the mol2/prep file to describe the
> topology
> of your ligand) to produce the prmtop and inpcrd files required by
> sander.
>
> I hope that makes sense.
>
> All the best
> Ross
>
>
> /\
> \/
> |\oss Walker
>
> | Assistant Research Professor |
> | San Diego Supercomputer Center |
> | Tel: +1 858 822 0854 | EMail:- ross_at_rosswalker.co.uk |
> | http://www.rosswalker.co.uk | PGP Key available on request |
>
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