[gmx-users] protein Aggregation using Gromacs

Ran Friedman r.friedman at bioc.uzh.ch
Wed May 12 12:27:34 CEST 2010

Hello again -

IMHO the best approach for any simulation study is to plan how the
simulation will be used to solve a specific scientific problem before
running the simulations, rather then the other way around. To clarify
what I wrote below, there's no algorithm I'm aware of where the input is
an MD simulation of a certain protein and the output is an aggregation
propensity of certain residues.

Having said that, simulations can be a useful tool to study amyloid
aggregation and even tendency of specific residues to aggregate first. A
useful approach was developed in the group where I work now, based on
the aggregation propensity of peptide sequences decomposed from the
whole protein:

Using your simulations, you can check if some residues are more prone to
lose their secondary structure as the temperature increases, which 
suggests that they are more likely to unfold. Do bear in mind though
that aggregation is a complex process which involves multimers. Unless
you show some correlation with experimental findings it will be
difficult to defend your conclusions.


shahid nayeem wrote:
> Hi
>  I have used TANGO Aggrescan, Zyggregator and other online tools but I
> am unable to find and pinpoint residue responsible for aggregation.
> Then I did MD simulation of the proteins with gromacs at different
> temperature. Now in this background I need  suggestion to analyse my
> MD trajectory.
> shahid Nayeem
> On 5/12/10, *Ran Friedman* <r.friedman at bioc.uzh.ch
> <mailto:r.friedman at bioc.uzh.ch>> wrote:
>     Hi,
>     There's no recipie to locate aggregation hot spots based on MD
>     simulations. There are many papers on simulations of protein and
>     peptide
>     aggregation from which you can draw some ideas, but bear in mind that
>     aggregation of more than very few and very small peptides is typically
>     much slower than what one can simulate using atomistic MD.
>     For a quick approach you can use sequence analysis tools, e.g., TANGO
>     http://tango.crg.es/
>     Good luck,
>     Ran
>     --
>     ------------------------------------------------------
>     Ran Friedman
>     Postdoctoral Fellow
>     Computational Structural Biology Group (A. Caflisch)
>     Department of Biochemistry
>     University of Zurich
>     Winterthurerstrasse 190
>     CH-8057 Zurich, Switzerland
>     Tel. +41-44-6355559
>     Email: r.friedman at bioc.uzh.ch <mailto:r.friedman at bioc.uzh.ch>
>     Skype: ran.friedman
>     ------------------------------------------------------
>     shahid nayeem wrote:
>     > Dear all
>     > What are the analysis tools which should be used on MD
>     trajectory file
>     > in order to find potential aggregation sites of a protein.
>     Anyone can
>     > tell me about specific resource material on use of Gromacs to
>     predict
>     > protein aggregation hot spots from MD trajectory anlysis.
>     > Shahid Nayeem

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