From: Brian Radak (bradak_at_anl.gov)
Date: Tue Apr 05 2016 - 09:42:27 CDT
Just my 2 cents:
I think you've hit upon the primary weakness of aMD; it's often too
blunt of a sampling tool, especially in dual boost mode. It also might
not be especially controversial to say that it is not a useful tool for
sampling association/dissociation.
If you have two distinct states that you know you are interested in,
then it is almost assuredly more useful and expedient to employ a more
specific biasing coordinate.
Regards,
Brian
On 04/05/2016 04:31 AM, Norman Geist wrote:
>
> Ahh, that’s a different thing. As the boost potential will also affect
> the protein, you might need to fix its structure (maybe CA atoms) so
> the boost is only active for your ligand. Also, you could prevent the
> short peptide from dissociation using a weak constraint.
>
> Norman Geist
>
> *Von:*sunyeping [mailto:sunyeping_at_aliyun.com]
> *Gesendet:* Dienstag, 5. April 2016 11:11
> *An:* namd-l <namd-l_at_ks.uiuc.edu>; Norman Geist
> <norman.geist_at_uni-greifswald.de>
> *Cc:* namd-l <namd-l_at_ks.uiuc.edu>
> *Betreff:* Re: AW: AW: namd-l: why does the transition seem to be
> irreversible in aMD
>
> Dear Norman,
>
> Maybe you are right, but I am not sure.
>
> The conformation 1 I mentioned corresponds to the state that both
> termini of a short peptide bind to a protein of two long chains, and
> the conformation 2 corresponds to the state that one terminus of the
> short peptide dissociates with and strecthes away from the protein.
>
> The transition from conformation 1 (the initial crystal structure)
> to conformation 2 can occur at a relatively smaller boost energy with
> the whole protein structure seeming to be normal. Increasing the boost
> energy leads to the distortion of the whole protein together with the
> transition from the conformation 1 to 2. It seems to me that the
> distortion or disorder is irrelevant to the transition, and it does
> not predict the transition paths, neither. So I can hardly believe
> that adding a larger boost energy can lead to the transition from the
> conformation 2 to 1. Instead, I tend to guess that a larger boost
> energy will lead to more serious distortion or even collapse of the
> protein (dissociation of the two long chains), or dissociation of the
> whole short peptide from the protein. I may presume that in a
> extremely entended aMD this collapse process could reverse, but I
> cannot afford such a long-time simulation. So it is important to
> design the simulation rationally.
>
> Best regards.
>
> Yeping
>
> ------------------------------------------------------------------
>
> From:Norman Geist <norman.geist_at_uni-greifswald.de
> <mailto:norman.geist_at_uni-greifswald.de>>
>
> Time:2016 Apr 5 (Tue) 16:07
>
> To:孙业平<sunyeping_at_aliyun.com <mailto:sunyeping_at_aliyun.com>>
>
> Cc:namd-l <namd-l_at_ks.uiuc.edu <mailto:namd-l_at_ks.uiuc.edu>>
>
> Subject:AW: AW: namd-l: why does the transition seem to be
> irreversible in aMD
>
> Usually that’s how conformational sampling is about to work. The
> structures that you call disordered or distorted are part of the
> conformational space and also part of the transition paths between
> intermediate local minima. You will have to sample some amount of
> data and analyze the probability of states e.g. by creating
> histograms of proper reaction coordinates like rgyr and mainchain
> hbonds and compute free energies from it. This will also tell you
> the amount of energy required to do the transition you mentioned.
>
> Norman Geist
>
> *Von:*sunyeping [mailto:sunyeping_at_aliyun.com]
> *Gesendet:* Dienstag, 5. April 2016 09:48
> *An:* namd-l <namd-l_at_ks.uiuc.edu <mailto:namd-l_at_ks.uiuc.edu>>;
> Norman Geist <norman.geist_at_uni-greifswald.de
> <mailto:norman.geist_at_uni-greifswald.de>>
> *Betreff:* Re: AW: namd-l: why does the transition seem to be
> irreversible in aMD
>
> Dear Norman,
>
> Thank you for your replay. You are right that the aMD is aimed at
> conformational sampling but I wish to see that transitions between
> the two conformation occur alternately. It seems that the
> transition from conformation 1 to conformation 2 is easy in my
> aMD, but not vice versa. However, if I keep increasing the boost
> energy, the whole protein structure becomes distorted and many
> structural motifs become disordered in addition to the
> conformational transition I am studying. So I guess simply
> increase the boost energy may be not a wise strategy.
>
> Best regards.
>
> Yeping
>
> From:Norman Geist <norman.geist_at_uni-greifswald.de
> <mailto:norman.geist_at_uni-greifswald.de>>
>
> Time:2016 Apr 5 (Tue) 15:30
>
> To:namd-l <namd-l_at_ks.uiuc.edu <mailto:namd-l_at_ks.uiuc.edu>>, 孙业平
> <sunyeping_at_aliyun.com <mailto:sunyeping_at_aliyun.com>>
>
> Subject:AW: namd-l: why does the transition seem to be
> irreversible in aMD
>
> Well If I’m correct, you don’t actually want your structure to get
> stucked in an aMD, as the main goal is to perfrom conformational
> sampling. So your boost potential might be too small to leave the
> rather stable structure your system ran into.
>
> Norman Geist
>
> *Von:*owner-namd-l_at_ks.uiuc.edu
> <mailto:owner-namd-l_at_ks.uiuc.edu>[mailto:owner-namd-l_at_ks.uiuc.edu]
> *Im Auftrag von *sunyeping
> *Gesendet:* Dienstag, 5. April 2016 05:21
> *An:* namd-l <namd-l_at_ks.uiuc.edu <mailto:namd-l_at_ks.uiuc.edu>>
> *Betreff:* namd-l: why does the transition seem to be irreversible
> in aMD
>
> Dear NAMD users,
>
> I ran an aMD with NAMD and observed a transition in my structure
> from conformation 1 to conformation 2 within 10 ns. However, when
> extending the simulation, I couldn't observe the reversion from
> conformation 2 to conformation 1. Since the aMD is done by adding
> an extra boost energy to the simulation system, does that mean
> that conformation 2 is located in the high energy contour in the
> potential surface? Is the aMD biased to sample the conformations
> in the high energy contour in the potential surface rather than
> those in low energy basins? What can be done to biasly sample
> conformations in low energy basins? To be specific, how could I
> realize the reversion from conformation 2 to conformation 1?
>
> Yeping
>
-- Brian Radak Postdoctoral Appointee Leadership Computing Facility Argonne National Laboratory 9700 South Cass Avenue, Bldg. 240 Argonne, IL 60439-4854 (630) 252-8643 brian.radak_at_anl.gov
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