AMBER Archive (2006)

Subject: Re: AMBER: Which one is the best force field for DNA?

From: Jiri Sponer (sponer_at_ncbr.chemi.muni.cz)
Date: Fri Apr 14 2006 - 12:08:34 CDT

Hi Vlad, it would be an interesting comparison. The K-turn
complex could be a little tricky to discriminate between
"healthy" changes and problems.
The charge disbalance of course is an issue.

All the best Jiri

> Hi Jiri,
>
> With ff99 I also have experience for the 15.5K/K-turn complex (although
> not so long simulations but still )... But I was wondering about using
> ff03 for such complexes, since it has a different charge derivation
> philosophy for nucleic acids and proteins. As I thought of it and Carlos
> and Tom stressed it here, it is likely that at the interface there might
> be some mis-balance .. but I am still curious whether somebody has
> actually done such comparisons between ff99 and ff03 for protein-DNA or
> protein-RNA compelxes and observed this ...
>
> Cheers
> vlad
>
>
>
> Jiri Sponer wrote:
>
> >Hi Vlad,
> >
> >as this are empirical force fields, the only way to
> >establish the accuracy limits is to have very many and long tests.
> >And couple of really high quality reference structures.
> >We do have (BJ 2004 Reblova et al) protein - RNA complex
> >(L25 vs 5S rRNA Loop E - Helix IV, ca 25 ns scale, 99 version).
> >It looks more or less OK, although not all individual H-bonds
> >were as in the x-ray. On the other side, it is a pretty rigid
> >system so it easily could be locked around the start geometry.
> >On the other side, some H-bonds were replaced say by water bridges,
> >which, frankly, is so tiny balance that it does not necessarily
> >mean a disagreement.
> >
> >If anyone else has experience with RNA-protein, I would be happy
> >to know.
> >
> >All the best Jiri
> >
> >
> >
> >>Hi Tom, Jiri, David, all ambers
> >>
> >>Now, what about ff03? According to your opinion, is it recommended to be
> >>used in protein-nucleic acids complex simulations? Or is it "safer" to
> >>stick to ff99 for that purpose? It would be interesting if anybody has
> >>done simulations of protein-RNA or protein-DNA complexes with ff03 and
> >>compared them to simulations done with ff99..
> >>
> >>cheers
> >>vlad
> >>
> >>
> >>
> >>Thomas E. Cheatham, III wrote:
> >>
> >>
> >>
> >>>>Well, I did read sometime ago Tom's review, maybe I missed (or I forgot)
> >>>>some of the information there so I'll read it again ...So, I didnt know
> >>>>that ff99 (thus also ff03) doses not include the ff98 changes. Is there
> >>>>a particular reason why those changes were not included in newer versions?
> >>>>
> >>>>
> >>>>
> >>>>
> >>>ff99 does contain a slightly modified set of the ff98 changes; they are
> >>>not exactly the same (which likely led to DAC's comments), but very
> >>>similar.
> >>>
> >>>In ff98, we adjusted angles related to chi and the sugar in an attempt to
> >>>improve helical twist (increase it slightly) and to increase chi. This
> >>>was successfully accomplished, yet, we appeared to lose some of the
> >>>favorable features of ff94 in relation to stabilization of A-DNA in mixed
> >>>water/ethanol and with highly charged cations (hexammine cobalt(III)).
> >>>So, in some sense, one cannot definitely state that ff98 is "better" than
> >>>ff94, just different in that it has a slightly improved overall helical
> >>>twist.
> >>>
> >>> Cornell ff98 ff99
> >>>CT-OS-CT-N* V3 1.15 0.383 0.383
> >>> V2 0.0 1.0 0.65
> >>>
> >>>OS-CT-CT-OS V3 0.144 0.144 0.144
> >>> V2 1.0 1.5 1.175
> >>>
> >>>OS-CT-N*-CK V2 0.5 pi 0.0 0.0
> >>>or CM V1 2.5 2.5 2.5
> >>>
> >>>(the "pi" denotes a phase of 180; all other phases are 0 and the numbers
> >>>shown are the peak heights).
> >>>
> >>>
> >>>
> >>>
> >>>
> >>>>If I may, as a short comment on this, I believe that it is important to
> >>>>be able to use the same ff for both proteins and nucleic acids (perhaps
> >>>>membranes also) as they do coexist and many simulations involve
> >>>>
> >>>>
> >>>>
> >>>>
> >>>As a general rule, you do want consistency between force fields such that
> >>>if you run proteins and nucleic acids or membranes, there is not a
> >>>mis-balance. However, with respect to the ff94->ff99, the only
> >>>differences are largely dihedral parameters and not the overall
> >>>philosophy. Equivalent methods were used to generate charges, van der
> >>>Waals parameters such that all of these variants are compatible. This is
> >>>not true when comparing ff94->ff99 with the polarizable ff02 or ff02EP or
> >>>the new charge derivation philosophy of ff03 where there could
> >>>be-- although this has not been shown to my knowledge-- misbalance.
> >>>
> >>>--tom
> >>>
> >>>\-/ Thomas E. Cheatham, III (Assistant Professor) College of Pharmacy
> >>>-/- Departments of Med. Chem. and of Pharmaceutics and Pharm. Chem.
> >>>/-\ Adjunct Asst Prof of Bioeng.; Center for High Performance Computing
> >>>\-/ University of Utah, 30 S 2000 E, SH 201, Salt Lake City, UT 84112
> >>>-/-
> >>>/-\ tec3_at_utah.edu (801) 587-9652; FAX: (801) 585-9119
> >>>\-/ BPRP295A http://www.chpc.utah.edu/~cheatham
> >>>-----------------------------------------------------------------------
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> >>>
> >>>
> >>>
> >>>
> >>--
> >>Dr. Vlad Cojocaru
> >>EML Research gGmbH
> >>Molecular and Cellular Modeling Group
> >>Schloss-Wolfsbrunnenweg 33
> >>69118 Heidelberg, Germany
> >>Phone: +49-6221-533266
> >>Fax: +49-6221-533298
> >>e-mail: Vlad.Cojocaru_at_eml-r.villa-bosch.de
> >>http://projects.villa-bosch.de/mcm/people/cojocaru/
> >>
> >>
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>
> --
> Dr. Vlad Cojocaru
> EML Research gGmbH
> Molecular and Cellular Modeling Group
> Schloss-Wolfsbrunnenweg 33
> 69118 Heidelberg, Germany
> Phone: +49-6221-533266
> Fax: +49-6221-533298
> e-mail: Vlad.Cojocaru_at_eml-r.villa-bosch.de
> http://projects.villa-bosch.de/mcm/people/cojocaru/
>
>
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