Re: Studying Folding of 870 Small Peptides. Computationally Feasible?

From: Nicholas M. Glykos (
Date: Mon Dec 19 2016 - 03:36:15 CST

Finding water-soluble and stably folded short peptides (10-20 aa) is
relatively rare and difficult. Even more so for randomly generated sequences.
So, in my mind, the real question is this : was the screen that you've
used actively selecting for folded peptides ? If not, then the
expectation would
be that the greatest majority of the peptides will behave like random coils
with only extremely short-lived stable conformers. If you are hoping
to capture
some biologically relevant conformation from such a disordered peptide, you're
possibly out of luck : the probability that you can meaningfully sample the
unfolded state of a 20-residue peptide with 6 us of simulation time, is
negligible. Maybe you could formulate the question you want to answer in such
a way that a different approach (for example, docking) would do the trick ?

My twocents.

> I have 870 small peptides (10-20aa each) for which I'm trying to get
> predicted structures. The reason I'm using NAMD and not something
> like Rosetta
> is because the length of these peptides and the fact that they have mimimal
> homology to any peptides in nature (since their sequences were randomly
> generated, and then they were ran through a screen) causes problems with the
> structure prediction programs I've tried. I decided to run PSIPRED to get
> predicted secondary structures, put each peptide in said secondary
> structure,
> and then run them through NAMD to see if the secondary structures come apart
> and/or if supersecondary structures form. I'm going to do the initial
> minimization in explicit solvent, but then since explicit solvent
> calculations
> are slower (is that true? I've also heard the opposite), I'm going to then
> switch to GBIS thereafter. I read that supersecondary structures can take up
> to 6 microseconds to form. Is running 870 peptides for 6 us
> feasible? Based on
> some preliminary runs, it seems like it'll require a ton of computational
> power and a ton of time. Granted, these tests were on CPU cores not
> GPU cores.
> I'm using the TACC Lonestar5 supercomputer by the way
> (
> <>). Anyways, do my
> ambitions seem reasonable or should I rethink some of the technical aspects
> (e.g. running for way less than 6 us instead)?

             Nicholas M. Glykos, Department of Molecular Biology
      and Genetics, Democritus University of Thrace, University Campus,
   Dragana, 68100 Alexandroupolis, Greece, Tel/Fax (office) +302551030620,
     Ext.77620, Tel (lab) +302551030615,

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