Hi Francois,
I understand Cieplak et al. paper did mention removing conformations with
Hbonds between sidechain and backbone atoms for amino acids. But for a sugar
ring with -OH groups on C2, C3, and C4, it is kind of difficult to avoid
intra-molecular Hbond geometrically. According to what you suggested,
should we artificially avoid that hydrogen bonding by partial optimization,
even it "should be" there?
Thanks,
Yun
On Wed, Sep 21, 2011 at 11:45 PM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Matthew, Yun,
>
> I think QM theory levels are different when one wishes to target a
> geometry, an energy, and a MEP.
>
> - For MEPs and for a non-polarizable/fixed charge model, HF/6-31G* is
> used to induced an implicit polarization
> see http://ambermd.org/doc6/html/AMBER-sh-19.4.html#sh-19.4
>
> - To get representative energy values and representative dE values
> between conformations high basis sets (triple zeta with multiple
> polarization functions and diffusion functions; and MP2 or even MP4
> (if one can afford it)) are recommended.
>
> - For _bio-organic_ molecules, to get an optimized geometry HF/6-31G**
> is quite basic, Yes, and using diffusion functions should lead to a
> better accuracy, Yes. However, there is _obviously_ a reason for this
> choice... Geometry optimization is carried out in gas phase, while MD
> simulations are done in condensed phase. Thus, the conditions in
> geometry optimization will never fit to these of the molecules in
> their experimental environment (i.e. partially or totally solvated;
> docked in a protein, etc...). Thus, a basic theory level is used in
> geometry optimization with several empirical rules (i) a big molecule
> is split into elementary building blocks to fully define to different
> conformations to be involved in charge derivation (ii) canonical
> intra-molecular hydrogen bonds are generally avoided (hydrogen bonds
> induce over-polarization). To avoid intra-molecular hydrogen bonds and
> overpolarization effect partial geometry optimization can be used (the
> 'ModRedundant' mode when using Gaussian as reported by Matthew below).
>
> Thus, is it really useful to add diffusion functions in geometry
> optimization in these conditions? I am not sure... The main idea here
> is to get an empirical/canonical conformation representative of what
> one chooses and computes charges for these conformations.
>
> This is the approach followed by Cieplak et al. in 1995 (HF/6-31G*)
> and by Duan et al. (HF/6-31G**) in geometry optimization almost 10
> years later.
>
> If you look at optimized geometry of monosaccharide units in R.E.DD.B.
> intra-molecular hydrogen bonds are generally avoided:
> See for instance (two conformations might be present in these PDB files):
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/mol1.pdb
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/mol8.pdb
>
> http://q4md-forcefieldtools.org/REDDB/projects/F-72/
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/mol1.pdb
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/mol2.pdb
>
>
> I think you can find information about hydrogen bonds, MEP
> computation, geometry optimization, energy values and dE in:
> http://www3.interscience.wiley.com/cgi-bin/abstract/109583237/ABSTRACT
> http://onlinelibrary.wiley.com/doi/10.1002/jcc.10349/abstract
> http://pubs.rsc.org/en/Content/ArticleLanding/2010/CP/c0cp00111b
>
> regards, Francois
>
>
> > As Francois noted, we use the MD ensemble to weight the charges towards
> > solution conformations. My only concern is your QM levels are a bit off.
> > For neutral sugars, we optimize and develop the ESP with a 6-31G* basis
> set
> > whereas for anionic systems 6-31++G** is used for optimization and ESP
> > calculations. The RESP weight is the same (0.01) either way and the rest
> of
> > the options you mentioned are correct. I would use a crystal geometry
> for
> > your pre-ensemble averaged charges (if available) or an optimized QM
> > structure.
>
>
>
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Received on Fri Sep 23 2011 - 23:00:02 PDT
