[gmx-users] REMD of IDPs

[Smith, Micholas D.]

Dear Yanhua,

Converting a sequence into a structure is itself an "open" problem in computational biology/biophysics. There are ways to generate potential structures if you also happen to have some restraints from NMR or other experiments (small-angle scattering or CD-Spectra) noted in the literature, but getting to the "native" fold is very challenging. One program that tries to address the sequence to structure problem is Rosetta ( http://robetta.bakerlab.org/ ). 

If you have a short IDP fragment (less than 20 residues), one thing you can do it use something like Schrodinger's Maestro program (its free from their webpage www.schrodinger.com) and use the molecule builder to "grow" the chain as a random coil (random phi-psi placement), save the PDB from it and then run MD at high temp to relax the structure into a potential starting structure. If it is longer, the IDP may have small structural segments (the chain is dominated by disorder but may have short-lived, meta-stable, secondary structure regions) in which case you can either try to build the molecule with a corresponding secondary structure distribution (using Maestro) or try using Rosetta and refine with energy minimization.

Good Luck! 

===================
Micholas Dean Smith, PhD.
Post-doctoral Research Associate
University of Tennessee/Oak Ridge National Laboratory
Center for Molecular Biophysics

________________________________________
From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of João Henriques <joao.henriques.32353 at gmail.com>
Sent: Friday, April 08, 2016 3:51 AM
To: Discussion list for GROMACS users
Subject: Re: [gmx-users] REMD of IDPs

​Dear Yanhua,

To my knowledge (prior to gromacs 5.X at least), there​ are no gromacs
tools able to turn a sequence into a PDB. The user must take care of that
pre-processing on his/her own. I work with IDPs quite a lot, so what I can
tell you is what I usually do. I take my fasta sequence and use PyMOL to
construct the PDB. Then I'm able to feed the PDB to pdb2gmx.

*I'm sure there are a million different ways of doing this, given that
there are so many different protein modelling tools out there.*

Here's one example using Histatin 5.

- On PyMOL's command line type the following (without the quotation marks):
"for aa in "AKRHHGYKRKFH": cmd._alt(string.lower(aa))"

- This builds a fully stretched Histatin 5 3D model which can be exported
as PDB.

- Make sure to use "-ignh" on pdb2gmx, as the resulting hydrogen atom names
are usually incompatible with the force fields I routinely use.

- It's also a good idea to use "-renum" on pdb2gmx as for some reason PyMOL
exports the PDB with residue numberings starting from no. 2.

Cheers,
João


On Fri, Apr 8, 2016 at 4:14 AM, YanhuaOuyang <15901283893 at 163.com> wrote:

> Hi, I have a sequence of an intrinsically disordered protein, I have no
> idea how to start my REMD with gromacs. e.g. how to convert my sequence
> into a pdb file
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