Hi Thomas!
I only count real atoms, it is like a "per degree of freedom" thing.
When I do implicit solvent I only use the boost on the dihedrals, that
would be iamd=2
Hope everything works fine :)
> Hi Romelia,
>
> Thank you for your suggestions. I believe they will save other people as
> well from "disoriented" experimentation with the aMD parameters.
>
> Each monomer has 80 residues and I 'm using the Amber99SB-NMR1-ILDN ff.
> One
> important detail I omitted is that my test simulations were done in
> implicit solvent because I get 7x fold speed up compared with the original
> system, which has TIP4P-Ew waters and ions and counts 134000 atoms in
> total. Today I ran a couple of ns in explicit solvent and noticed that the
> dimer is more stable, actually it doesn't move that much with the
> suggested
> parameter values. I will carry out more tests in explicit solvent and let
> you know about the outcome.
>
> Just one last question, when I estimate Ep and aP values should I count
> each TIP4P-Ew water as 4 atoms or as 3? So far I counted each water as 4
> atoms.
>
> Thank you so much!
>
> Thomas
>
>
>
>
>
>
>
> On 19 November 2012 20:20, Romelia Salomon <romelia.caltech.edu> wrote:
>
>> 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
>>
>>
>
>
> --
>
> ======================================================================
>
> 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/
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
****************************************
Romelia Salomon
Walker Group
398 San Diego Supercomputing Center
UC San Diego
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Nov 19 2012 - 14:00:02 PST
