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

From: Brian Radak (
Date: Mon Dec 19 2016 - 09:32:10 CST

Although I think JC and Peter are correct - a folding MD simulation may
not be appropriate/worth the effort - there might be some hope.

Although really, IMO, that paper just shows that with simulated
tempering you can access the power of T-REMD at a fraction of the cost.

On 12/19/2016 03:36 AM, Nicholas M. Glykos wrote:
> 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)?

Brian Radak
Postdoctoral Appointee
Leadership Computing Facility
Argonne National Laboratory
9700 South Cass Avenue, Bldg. 240
Argonne, IL 60439-4854
(630) 252-8643

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