Re: AMBER: MD & folding

From: Bimo Ario Tejo <>
Date: Tue, 2 Nov 2004 08:26:09 +0100 (MET)

Hello Bo:

1. I would say the value of 1.41 +/- 0.21 A and 1.63 +/- 0.32 A is not
significantly different if you look at the deviation values.

2. You could not expect to see any protein unfolding in 1 ns timescale using
MD. What CD shows you is an averaged structure of your molecule in seconds
(or even minutes) timescale. I would suggest you to prolong your
simulations, at least in microseconds timescale.

2. You did not neutralize your system. Although this is not related with
protein folding, please consider the effect of charged system if you are
using PBC system.

Best wishes,
> Hello, Amber:
> I use molecular dynamic simulation to explore the pH effect on the
> protein folding. The purpose is to find out the most flexible regions on
> my target protein. The runs were set up at two conditions: pH 7.0 and pH
> 2.0. For the run at pH 2.0, all Glu, Asp and His residues were changed to
> their protonation states. For the run at pH 7.0, no change was made on
> these residues. When I analysis the results from 1 ns simulations,
> something came out very strange. The RSMD curve of pH 2.0 is at the
> similar level as that of pH 7.0. The RMSD values at pH 2.0 are even
> smaller that those at pH 7.0. The mean value of RSMD at pH 2.0 is 1.41
> +_ 0.21 ┼. The mean of RSMD at pH 7.0 is 1.63+_ 0.32 ┼.
> I also did the trajectories analysis. I selected the frames from the time
> points with the lowest energy levels, saved the individual frames and
> clustered them together. I didn’t see significant changes on the overall
> structures. When I examined atom distances of some target salt-bridges
> in the protein model, I observed that some, but not all, had larger
> values at pH 2.0 than that at pH 7.0.
> From the literatures, many indicated that significant changes on the
> protein structures were observed with MD simulation under certain
> conditions, such as high temperature and low pHs. From CD studies, the
> protein I used for the MD simulation was observed losing its tertiary
> structure at acid conditions (pH 2.0 – 4.5), but some of secondary
> structures remained. A ‘molten structure’ has been proposed for the
> conformation of this protein at low pH conditions.
> The results from my MD simulations showed that the protein is quite
> stable at the low pH condition. This is controversial to the results from
> experimental studies. I am wandering if I set my MD running conditions
> reasonable or not. I use AMBER7. The protein models were solvated with
> WATERBOX 216 with 10 ┼ distance. The systems were not neutralized. At pH
> 7.0, the overall charge of the model is +2.0. At pH 4.0, the overall
> charge is +32. I use ff94 force filed plus the modified
> frcmod.mod_phipsi.1 from Amber website. I have included my MD input files
> and the RSMD plots as attachments.
> Thank you for your advices and comments.
> Regards
> Bo

Bimo Ario Tejo, Ph.D
Department of Biochemistry
Faculty of Biotechnology and Biomolecular Sciences
Universiti Putra Malaysia
43400 Serdang
fax: +60-3-89430913
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Received on Tue Nov 02 2004 - 07:53:00 PST
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