AMBER Archive (2006)

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

From: Vlad Cojocaru (Vlad.Cojocaru_at_eml-r.villa-bosch.de)
Date: Fri Apr 14 2006 - 12:01:27 CDT

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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