From: Francesco Pietra (francesco.pietra_at_accademialucchese.it)
Date: Tue May 08 2012 - 01:59:49 CDT
---------- Forwarded message ----------
From: Francesco Pietra <francesco.pietra_at_accademialucchese.it>
Date: Tue, May 8, 2012 at 8:50 AM
Subject: Re: namd-l: stereo-chemical inversion during MD
To: Norman Geist <norman.geist_at_uni-greifswald.de>
I wonder whether you know about
Stereochemical errors and their implications
for molecular dynamics simulations
Eduard Schreiner1, Leonardo G Trabuco2, Peter L Freddolino3 and Klaus Schulten4*
Abstract
Background: Biological molecules are often asymmetric with respect to
stereochemistry, and correct
stereochemistry is essential to their function. Molecular dynamics
simulations of biomolecules have increasingly
become an integral part of biophysical research. However,
stereochemical errors in biomolecular structures can
have a dramatic impact on the results of simulations.
Results: Here we illustrate the effects that chirality and peptide
bond configuration flips may have on the
secondary structure of proteins throughout a simulation. We also
analyze the most common sources of
stereochemical errors in biomolecular structures and present software
tools to identify, correct, and prevent
stereochemical errors in molecular dynamics simulations of biomolecules.
Conclusions: Use of the tools presented here should become a standard
step in the preparation of biomolecular
simulations and in the generation of predicted structural models for
proteins and nucleic acids.
Schreiner et al. BMC Bioinformatics 2011, 12:190
http://www.biomedcentral.com/1471-2105/12/190
Regards by chiendarret
On Tue, May 8, 2012 at 8:01 AM, Norman Geist
<norman.geist_at_uni-greifswald.de> 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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