Re: Re: AW: stereo-chemical inversion during MD

From: Axel Kohlmeyer (akohlmey_at_gmail.com)
Date: Tue May 08 2012 - 08:33:03 CDT

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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>

-- 
Dr. Axel Kohlmeyer
akohlmey_at_gmail.com  http://goo.gl/1wk0
College of Science and Technology
Temple University, Philadelphia PA, USA.

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