Dear Yong,
Thanks a lot for following up on this ... It is very useful to clarify
all my questions regarding this issue. I have another small question. I
have been doing some simulations of protein-ligand (small molecule)
complex and use ff03 for the protein and HF/6-31g* charges for the
ligang (derived with RED II - GAMESS). From your experience, would you
think that even for small molecules one should be strict and derive
charges according to the ff03 model? ...
And just a short follow up on this, can one use the antechamber derived
am1-bcc charges for small ligands in combination with ff03 for proteins?
Thanks again
Best wishes
vlad
Yong Duan wrote:
>To follow up on this thread, Carlos is absolutely right that one should not
>simply mix two charge models.
>
>However, if the concern is only limited to the terminal residues, the answer
>is much less a clear cut. Although ff03 charges were based on a different
>model, they are reasonably compatible with the Cornell charges, as far as
>the dipole moments and other simple measures are concerned. In our lab, we
>simply use the ff94 charges for the terminal groups for most of the
>simulations. However, in the cases where the terminal charges are
>anticipated to play crucial roles, we try to refit the charges. For example,
>when we try to compare the energies of di-peptides against QM energies, we
>use the ff03 charges for the amino acids and fit the charges for the
>terminal groups. In this case, the terminal groups do have different charges
>according to the amino acid they are attached to. But such an approach is
>considered unecessary for larger peptides. If the application is to
>proteins, I'd be less concerned.
>
>Please also keep in mind that the charges of the terminal groups in the
>Cornell charge set were obtained by a retro-fitting using a combined-fit
>scheme (with NMA?), rather than from the fitting of the individual terminal
>amino acids.
>
>Hope this helps. Please do let us know if you have any further questions.
>
>yong
>
>
>
>>-----Original Message-----
>>From: owner-amber.scripps.edu
>>[mailto:owner-amber.scripps.edu] On Behalf Of Carlos Simmerling
>>Sent: Thursday, August 03, 2006 3:59 AM
>>To: amber.scripps.edu
>>Subject: AMBER: ff03 and ff99SB force fields
>>
>>
>>Vlad,
>>I'm replying off the list to send you the manuscript
>>for the ff99SB article that is in press at Proteins.
>>For the purposes of the archive, I'll clarify my comments on
>>compatibility and invite Yong Duan to join in and give us the
>>benefit of his much more extensive experience with ff03.
>>
>>I think that one has to be extremely careful mixing force fields.
>>To my knowledge it has not been demonstrated that hydrogen
>>bonds (for example) between ff94 and ff03 backbone charges
>>are the same as ones between pairs of ff03 groups. Since the charge
>>model fundamentally differs (or else why is there a need for
>>ff03?) one
>>should probably not mix them in a single simulation. It would be like
>>taking
>>charmm parameters and using with ff94- both are internally
>>consistent but
>>you need to carefully test whether they have the same intra-
>>and inter-
>>force field interactions.This is important to me since one of
>>my projects
>>involves protein/DNA complexes and I don't want to do all of the
>>extensive testing needed to make sure that the DNA parameters will
>>work well with ff03 proteins when I know that ff99SB doesn't have
>>that concern.Another concern about ff03 is that not all of the
>>torsions were refit. I don't mean to criticize Duan's effort at all,
>>just to
>>point out that I think ff03 is still a work in progress (and
>>a good one).
>>
>>Our ff99SB paper is in press at Proteins. I believe that we
>>do as well
>>or even
>>slightly better than ff03 for the things you ask about. Both
>>ff99SB and
>>ff03 are
>>much better than any of the other Amber variants that we
>>tested. In addition
>>to secondary structure bias, almost all of the other have very serious
>>problems with their glycine parameters.
>>Carlos
>>
>>Vlad Cojocaru wrote:
>>
>>
>>
>>>Dear Carlos,
>>>
>>>I am following closely this discussion about the incompatibilities
>>>between ff03 and the other amber force field versions. So,
>>>
>>>
>>first I would
>>
>>
>>>like to ask you, what do you actually mean by "imbalance in
>>>
>>>
>>elecrostatics".
>>
>>
>>>Furthermore, the paper describing the ff03 speaks of
>>>
>>>
>>correlation between
>>
>>
>>>the "new" charges and the old charges and claims that at
>>>
>>>
>>least in cases
>>
>>
>>>of ligand-protein interactions, there should be no reason not to use
>>>"old" ligand charges with "new" charges for protein residues.
>>>
>>>Moreover, when ff03 is loaded into Leap, only non-terminal
>>>
>>>
>>amino acids
>>
>>
>>>are loaded from the new library, while N-terminal and
>>>
>>>
>>C-terminal AA are
>>
>>
>>>loaded from the old 94 libraries. So, isnt that
>>>
>>>
>>inconssistent? Or is it
>>
>>
>>>believed that non-terminal residues are not that important?...
>>>
>>>The reason for asking these questions, is because according
>>>
>>>
>>to studies
>>
>>
>>>that have been done in our group (not by me), ff03 seems to be by far
>>>the best version if one is interested in lifetimes and stabilities of
>>>secondary structural elements (ff99SB was not tested). Is there any
>>>reference which compares ff99SB with ff03 in that respect?
>>>
>>>Best wishes
>>>vlad
>>>
>>>Carlos Simmerling wrote:
>>>
>>>
>>>
>>>
>>>
>>>>due to the different charge model, you will need to find parameters
>>>>developed specifically for ff03. using other sets would result in
>>>>imbalance in electrostatics between different groups and is not
>>>>a good idea. On the other hand, ff94, ff96, ff99 and several other
>>>>variants such as our lab's ff99SB and parameters from Garcia and
>>>>Pande all use the same charge model and will work with any
>>>>
>>>>
>>parameters
>>
>>
>>>>developed for ff94.
>>>>
>>>>Zu Thur Yew wrote:
>>>>
>>>>
>>>>
>>>>
>>>>
>>>>>Hi,
>>>>>
>>>>>I would like ask if there are any pTHR parameters suitable for use
>>>>>with ff03?
>>>>>
>>>>>I know there are parms developed in the same way as ff94/ff99...the
>>>>>charges for normal THR in ff99 & ff03 seems quite different...
>>>>>
>>>>>has anyone any experience using these parms with ff03?
>>>>>
>>>>>
>>Would problems
>>
>>
>>>>>be expected if these parameters are used with ff03?
>>>>>
>>>>>Any advice would be most appreciated!
>>>>>
>>>>>Many Thanks,
>>>>>
>>>>>ZT
>>>>>
>>>>>-----------------------------------------------------------
>>>>>
>>>>>
>>------------
>>
>>
>>>>>The AMBER Mail Reflector
>>>>>To post, send mail to amber.scripps.edu
>>>>>To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
>>>>>
>>>>>
>>>>>
>>>>>
>>>>------------------------------------------------------------
>>>>
>>>>
>>-----------
>>
>>
>>>>The AMBER Mail Reflector
>>>>To post, send mail to amber.scripps.edu
>>>>To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
>>>>
>>>>
>>>>
>>>>
>>>>
>>>
>>>
>>>
>>>
>>--------------------------------------------------------------
>>---------
>>The AMBER Mail Reflector
>>To post, send mail to amber.scripps.edu
>>To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
>>
>>
>>
>
>-----------------------------------------------------------------------
>The AMBER Mail Reflector
>To post, send mail to amber.scripps.edu
>To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
>
>
>
--
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.eml-r.villa-bosch.de
http://projects.villa-bosch.de/mcm/people/cojocaru/
-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber.scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo.scripps.edu
Received on Sun Aug 06 2006 - 06:07:14 PDT
