Note, that it can not help if
1) receptor model is inadequate
2) ligand is parametrized not accurately
3) initial position of a ligand is really poor
For me, 14 ns it is rather long time in Amber when using explicit
solvent so I am just afraid that you will waste time if you extend the
simulation. May be it is a good idea to start with a different ligand
conformation..
Can anyone suggest is it the the case when REMD is appropriate since
this method is new for me?
On Wed, Mar 16, 2011 at 8:52 PM, George Tzotzos <gtzotzos.me.com> wrote:
> Thanks Dmitri,
>
> I'll try to extend the simulation time beyond 14ns and see what happens.
>
>
> On Mar 16, 2011, at 4:47 PM, Dmitry Nilov wrote:
>
>> How long did you simulate?
>> In what a way receptor model was obtained?
>> Note, that ligand just can stick in a high energy minima during the
>> simulation and crossing of energy barrierrs to bind appropriately can
>> be hardly probable on the time scale of your simulation.
>>
>> On Wed, Mar 16, 2011 at 6:25 PM, George Tzotzos <gtzotzos.me.com> wrote:
>>> Indeed. I've run production trajectories. In fact, I'm trying to reproduce some literature results. In my simulation the ligand forms Hbonds with a sub-set of residues reported in a published paper. This prompted me to suggest that my simulation does not explore the complete binding site.
>>>
>>>
>>>
>>>
>>>
>>> On Mar 16, 2011, at 4:10 PM, Dmitry Nilov wrote:
>>>
>>>> Hope you will perform conformational search by production trajectory
>>>> run without any restraints. Preliminary equilibration stages is just
>>>> for equilibration of the starting system).
>>>>
>>>> On Wed, Mar 16, 2011 at 5:37 PM, George Tzotzos <gtzotzos.me.com> wrote:
>>>>> Hi everybody,
>>>>>
>>>>> I've been running simulations involving ligand-receptor complexes and found that my ligand does not explore the complete conformational space of the binding pocket.
>>>>>
>>>>> I have applied weak restraints on the complex by analogy to tutorial 3, that is restraint_wt=2.0 (http://ambermd.org/tutorials/advanced/tutorial3/section1.htm). The restraints was applied both on the protein residues and the ligand during both density and pressure equilibration. My question is whether removing the restraints on the ligand during pressure equilibration would result in a more effective search of conformational space.
>>>>>
>>>>> Thanks in advance for any suggestions on the matter.
>>>>>
>>>>> Regards
>>>>>
>>>>> George
>>>>>
>>>>> _______________________________________________
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>>>>> AMBER.ambermd.org
>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>
>>>>
>>>>
>>>>
>>>> --
>>>> Dmitry Nilov,
>>>> Faculty of Bioengineering and Bioinformatics,
>>>> Lomonosov Moscow State University
>>>>
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>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>
>>>
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>>>
>>
>>
>>
>> --
>> Dmitry Nilov,
>> Faculty of Bioengineering and Bioinformatics,
>> Lomonosov Moscow State University
>>
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>
>
> _______________________________________________
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>
--
Dmitry Nilov,
Faculty of Bioengineering and Bioinformatics,
Lomonosov Moscow State University
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Received on Wed Mar 16 2011 - 12:30:02 PDT
