Re: AW: stereo-chemical inversion during MD

From: Branko (bdrakuli_at_chem.bg.ac.rs)
Date: Tue May 08 2012 - 10:51:46 CDT

Axel,

This is valuable information, still I didn't faced with similar
situation so far. Also, I can suppose than something like this is
possible for sp3 N, still cannot imagine such high energy intermediate
of sp3 C. On the other hand Gordon simulate one amino acid in explicit
solvent and obtain stereochemical inversion. Did he start with conformer
of unrealistic high energy. In protein, surroundings can constrain this
residue in such conformation, still think that something in initial
settings did not work perfectly. Maybe high temperature or similar, also
there is no information about origin of the starting protein, taken from
the PDB, modeled. Gordon state that can overcome problem by 'increasing
the di-electric or decreasing the partial charges on the ammonium
hydrogens'. Is there some metal ions in vicinity. Also are free amino
acid is comparable with the same one bound in the protein; even if this
is C terminal amino acid 'NH2' should be part of amide bond - so this
isn't NH3+...

Branko

On 5/8/2012 3:33 PM, Axel Kohlmeyer wrote:
> On Tue, May 8, 2012 at 4:26 AM, Branko<bdrakuli_at_chem.bg.ac.rs> wrote:
>> Stereochemical inversion implies bond breaking and bond making, and this is
>> not possible by molecular dynamics and using all atoms force fields. It is
> i beg to differ. stereochemical inversion is quite possible
> without bond breaking and particularly with a classical
> model. all you need is to go through a very high-energy
> intermediate. and particularly this last condition is what
> makes it particularly possible for a classical model, since
> bonds do *not* break in this case. when setting up a
> simulation and trying to get it to equilibrium, these kind
> of conditions can happen (and they happen more frequently
> than people suspect).
>
> just consider the case of a asymmetrically substituted
> methane. all you need is a conformation where all substituents
> are in the same plane as the central carbon atom. depending
> on how the planar symmetry is broken, you will get a
> different stereo isomer.
>
> VMD ships with two plugins that help to detect such artefacts:
>
> http://www.ks.uiuc.edu/Research/vmd/plugins/chirality/
> http://www.ks.uiuc.edu/Research/vmd/plugins/cispeptide/
>
> cheers,
> axel.
>> advisable to carefully check your input PDB file, residue name, atoms etc.
>>
>>
>> On 5/8/2012 8:01 AM, Norman Geist wrote:
>>
>> Hi Gordon,
>>
>>
>>
>> I’m not a specialist for biochemistry, but what you say could make sense as
>> the minimization looks for the best energy conformation. It could be, that
>> this angle is a better energy conformation for a particular system. But when
>> it’s bounded to other residues, it would maybe interfere with other side
>> chains and so would stay with the original angle. That would be easy to try
>> out. I can hardly imagine that the minimization algorithm can work against
>> the FF parameters.
>>
>>
>>
>> Norman Geist.
>>
>>
>>
>> Von: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] Im Auftrag
>> von Gordon Wells
>> Gesendet: Montag, 7. Mai 2012 19:01
>> An: namd-l_at_ks.uiuc.edu
>> Betreff: namd-l: stereo-chemical inversion during MD
>>
>>
>>
>> Hi All
>>
>>
>>
>> I've encountered a strange situation when simulating a particular
>> conformation of L-Glu. During minimisation the bond angle between the
>> carboxyl-C, C-alpha and amino-N decreases from 112° to 89°. When this is
>> subsequently used for MD there is often a stereo-chemical inversion around
>> the C-alpha. I see this when simulating the system in its original protein
>> complex and free in solution (TIP3 solvent for both).
>>
>>
>>
>> I can prevent it by using a very short minimisation (50 instead of 1000
>> steps), increasing the di-electric or decreasing the partial charges on the
>> ammonium hydrogens. Nonetheless, I'm sure this strained conformation
>> shouldn't be produced in the first place (I'm not able to replicate this
>> behaviour in macromodal or desmond) The force between the carboxyl oxygen
>> (nearest to the ammonium moiety) and the ammonium hydrogens seems to be too
>> high.
>>
>>
>>
>> I've attached before and after pdbs of the free L-glu. I get the distorted
>> conformation from the following namd input (with and without pbc):
>>
>>
>>
>> coordinates LGlu_autopsf.pdb
>>
>> structure LGlu_autopsf.psf
>>
>>
>>
>> paratypecharmm on
>>
>> parameters par_all27_prot_lipid_na.inp
>>
>>
>>
>> outputname minall-lglu-only
>>
>> binaryoutput yes
>>
>> outputenergies 25
>>
>>
>>
>> switching on
>>
>> cutoff 12
>>
>> switchdist 10
>>
>> pairlistdist 14
>>
>> exclude 1-4
>>
>>
>>
>> fixedAtoms off
>>
>>
>>
>> numsteps 1000
>>
>> dielectric 1
>>
>> minimization on
>>
>>
>>
>> Is this forcefield related, bad input file or possibly a bug in NAMD?
>>
>>
>> -- max(∫(εὐδαιμονία)dt)
>>
>> Dr Gordon Wells
>> Chemistry Department
>>
>> Emory University
>>
>> Atlanta, Georgia, USA
>>
>>
>>
>>
>>
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