AMBER Archive (2006)

Subject: Re: AMBER: double stranded polyribocytidylic acid

From: Jiri Sponer (sponer_at_ncbr.chemi.muni.cz)
Date: Wed Feb 15 2006 - 11:46:27 CST

Hi Bill,

it could be very interesting (scientifically) whether it can
exist or not as a duplex, at least locally.
In any case fiber structures may contain errors of that
kind you describe.

What I found suspicious in Kateryna's description is the
vertical distance of base pairs 3.11 A, since each base
pair is protonated, and thus I would expect increased
vertical separation. Nothing prevents to do so in
duplex. (May be there is base pair inclination of
that kind like in A-form, which would produce
closer separation along the global helix axis).

Alternative way is to take the i-tetraplex, to remove
one of its self-intercalated duplexes, and let the rest
relaxe as duplex via MD.

An open issue is, I think, still the structure of polyA.

Best wishes, Jiri

Hi Jiri,
>
> The distortion during minimization sounds like it could be more
> due to model-building artifacts than a basic wrong structure, though
> the latter may well also be the case. In such circumstances it would
> be interesting to see if proper equilibration could put the duplex in
> a local minimum - how long might it last?
>
> Bill
>
> > Hi Bill,
> > in this case she likely attempts to simulate a nonexisting
> > molecule. The difraction experiment on polyC is old, not much data, and
> > oligoC in recent experiments form selfintercalated tetraplexes,
> > not duplexes,
> > no duplex has ever been seen at atomic resolution.
> >
> > Jiri
> >
> >
> > > > I'm trying to perform the simulation of double stranded
> > > > polyribocytidylic acid but I haven't succeded yet.
> > > > I start with the structure built according to the Langridge and Rich
> > > > data(Nature,1963): helical rise=3.11 A, helical twist=30 degrees, parralel
> > > > strands, each strand consisting of alternating cytosine, protonated
> > > > cytosine residues, so that each pair of the double helix contains one
> > > > protonated cytosine. But even during the minimization my structure
> > > > distorts greatly: bases in pairs become nonplanar and the whole
> > > > structure looks rather like two single-stranded helices twisted one on
> > > > the another, than a double stranded helix. The more steps of the
> > > > minimization I perform, the more distorted structure I obtain.
> > >
> > > Small, relatively inconsequential errors in the starting structure
> > > can induce such problems. Energy minimization is not the best
> > > procedure for fixing the model - better would be to use positional
> > > restraints on the bases and run dynamics in vacuum, e.g. at 10-100K.
> > > (Because of the classic local minimum problem.)
> > >
> > > It is quite impressive to see a nucleic acid backbone equilibrate
> > > under such conditions. After this procedure, solvate, minimize
> > > 100-500 steps, and continue with careful equilibration of volume
> > > and temperature.
> > >
> > > Bill
> > >
> -----------------------------------------------------------------------
> The AMBER Mail Reflector
> To post, send mail to amber_at_scripps.edu
> To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu
>
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu