Hi Thomas
Try using these parameters:
Ed=Ed_average+3.5*ResNum (smaller per residue boost which will be a
smaller Ed and less agressive)
aD=3.5*ResNum*0.25 (larger scale factor which will be a larger alpha
which will be LESS agressive)
Ep=Ep_average+0.16*AtomNum (this is probably okay)
aP=0.16*AtomNum (this is okay)
What FF is you are using and how many residues is one of the monomers? In
a collaboration we have some runs with HIVPR (which is a dimer) with
ff99SB and using the above suggested parameters and we have not seen a
separation of the dimer. You should see more movement in your structure
and that the secondary structures are change a bit, but they should not
unfold in an unexpected way (I am working on a protein that undergoes a
large transition and part of it involves the unfolding of an alpha helix).
Is it an explicit solvent or GB?
Maybe it is in the way the system is being initialized.
Best,
Romelia
> Hi Romelia,
>
> It happens both, but the dissociation of the dimer is more noticeable. The
> dimer is a helical bundle and as the helices start to bend it dissociates.
>
> thanks,
> Thomas
>
>
> On 19 November 2012 18:35, Romelia Salomon <romelia.caltech.edu> wrote:
>
>> Dear Thomas
>>
>> One quick question first, is it unfolding the secondary structures or
>> separating the two components of the dimer?
>>
>> Best wishes,
>>
>> Romelia
>>
>> > Dear Romelia and other AMBER users/developers,
>> >
>> > Thanks for the clarification. I have tried the rule of thump to select
>> E
>> > and alpha values, which is described both in the recent paper you
>> cited
>> > and
>> > the manual. Namely, to decide the dihedral boost parameters (Ed, aD)
>> and
>> > the potential boost parameters (Ep, aP) I did:
>> >
>> > Ed=Ed_average+4*ResNum
>> > aD=4*ResNum*0.2
>> > Ep=Ep_average+0.16*AtomNum
>> > aP=0.16*AtomNum
>> >
>> > However, these parameter values lead to the unfolding of my protein
>> dimer.
>> > I have also tried setting aD=4*ResNum*0.4 but I still observe the same
>> > effect.
>> > How would you recommend making the boost smoother? By increasing just
>> the
>> > alpha values? Do I need to increase both of them?
>> >
>> > thanks in advance,
>> > Thomas
>> >
>> >
>> >
>> >
>> > On 27 September 2012 01:27, Romelia Salomon <romelia.caltech.edu>
>> wrote:
>> >
>> >> Hi Thomas
>> >>
>> >> I added comments to your questions bellow.
>> >>
>> >> > Dear Amber users,
>> >> >
>> >> > I want to monitor the dynamics between a hetero-dimeric helical
>> bundle
>> >> and
>> >> > a peptide. It is believed that the peptide binds at the
>> >> protein-protein
>> >> interface of the dimer and unwinds the helix of one of the
>> components.
>> >> For
>> >> > this purpose I am considering accelerated MD (aMD) but have some
>> >> queries
>> >> about it:
>> >> >
>> >> > 1. Unlike Metadynamics, the bias in the potential is not history
>> >> dependent,
>> >> > therefore the system may explore multiple times the same area of
>> >> conformational space. Is this correct?
>> >>
>> >> This is correct, AMD will make it more probable to move out of deep
>> >> stable
>> >> basins in the conformational space and there is no mechanism to
>> prevent
>> >> it
>> >> from going back.
>> >>
>> >> >
>> >> > 2. Is it possible to find the predominant conformations of the
>> complex
>> >> from
>> >> > an aMD trajectory, namely the ones that we would expect to observe
>> the
>> >> most
>> >> > in an unbiased MD trajectory?
>> >>
>> >> Yes, what you will get in the end of the AMD calculation is a state
>> >> distribution, that although is not the unbiased (canonical) one, it
>> >> still
>> >> holds some resemblance to it. AMD distributions can be re-weighted to
>> >> produce Boltzmann distributions.
>> >>
>> >> Please refer to these papers for more information.
>> >> (a recent paper we just published on the GPU implementation of AMD)
>> >> http://pubs.acs.org/doi/abs/10.1021/ct300284c
>> >> (one of the main papers for this method)
>> >> http://www.cse.nd.edu/~izaguirr/HaMM04.pdf
>> >>
>> >>
>> >> I hope this helps, let me know if you need more information.
>> >>
>> >> Best,
>> >>
>> >> Romelia
>> >
>>
>>
>> --
>> ****************************************
>> Romelia Salomon
>> Walker Group
>> 398 San Diego Supercomputing Center
>> UC San Diego
>>
>>
>
>
> --
>
> ======================================================================
>
> Thomas Evangelidis
>
> PhD student
> University of Athens
> Faculty of Pharmacy
> Department of Pharmaceutical Chemistry
> Panepistimioupoli-Zografou
> 157 71 Athens
> GREECE
>
> email: tevang.pharm.uoa.gr
>
> tevang3.gmail.com
>
>
> website: https://sites.google.com/site/thomasevangelidishomepage/
>
--
****************************************
Romelia Salomon
Walker Group
398 San Diego Supercomputing Center
UC San Diego
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Received on Mon Nov 19 2012 - 10:30:02 PST
