Re: [AMBER] Simulating a Protein - cyclic peptide complex - question

From: Dr. Anselm Horn via AMBER <amber.ambermd.org>
Date: Fri, 11 Nov 2022 10:47:18 +0100

Suchetana,

when I understood your question correctly, then you are wondering how to
create a system with a large protein and a small cyclic peptide using
leap, since the loadPDBusingSeq command would be rather tedious for the
protein part, and otherwise the information about the bond in the cyclic
peptide would be lost.

Although I've not tried it out, I'd suggest to create two separate
units, one for the protein via loadpdb and one for the cyclic peptide
via loadpdbusingseq, and then use the combine command to create a third
unit, which is a combination of both.
AFAIK, leap does not change the input coordinates, so you should be save
there.

Technically, you'd split up your input pdb file, which contains the
protein (and other stuff like organic ligands etc) and the cyclic
peptide in the correct mutual orientation, into two separate input pdb
files, load them into leap, combine them into a new complex unit, and
then proceed with solvation and (counter) ion addition.

If you try that out, I'd be happy to learn, whether my suggestion worked
(vide infra).

Best,

Anselm

Bioinformatik | NHR.FAU
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Germany

# -------------------
# Start of leap input
# Protein complex with cyclic peptide ligand (to be validated)
# 0, Parameter section
source leaprc.protein.ff14SB
source leaprc.gaff
source leaprc.water.tip3p
loadamberparams xyz.frcmod
loadamberparams abc.frcmod
loadoff xyz.lib
loadoff abc.lib
# 1, Cyclic peptide
seq = { A B C D E F G }
cycpep = loadPDBusingseq peptide.pdb seq
bond cycpep.1.N cycpep.8.C
# 2, Protein
protein = loadpdb my-protein_with-organic-ligands.pdb
# 3, Complex
complex = combine { protein cycpep }
solvatebox complex TIP3PBOX 15.0
check complex
charge complex
addions complex Na+ 0
addions complex Cl- 0
# 4, Output
savepdb complex complex_wat_ion_out.pdb
saveAmberParm complex complex_wat_ion.top peptide_wat_ion.crd
quit
# End of leap input
# -------------------



Am 11.11.2022 um 02:02 schrieb Suchetana Gupta via AMBER:
> Dear Amber Users
> I am trying to simulate a protein-cyclic peptide complex and have a basic
> question.
> When I simulated the cyclic peptide only, the leap.in file had the lines
> like:
>
> source leaprc.protein.ff14SB
> source leaprc.gaff
> source leaprc.water.tip3p
> loadamberparams xyz.frcmod
> loadamberparams abc.frcmod
> loadoff xyz.lib
> loadoff abc.lib
> seq = { A B C D E F G }
> cycpep = loadPDBusingseq peptide.pdb seq
> bond cycpep.1.N cycpep.8.C
> solvatebox cycpep TIP3PBOX 15.0
> check cycpep
> charge cycpep
> addions cycpep Na+ 0
> addions cycpep Cl- 0
> savepdb cycpep peptide_wat_out.pdb
> saveAmberParm cycpep peptide_wat.top peptide_wat.crd
> quit
>
>
> My question is, when I simulate the peptide-protein complex, how do I frame
> the leap input file? I am concerned about the loadPDB part. How do I load
> the PDB file of the complex while also taking care that the cyclic bond
> remains intact? The complex PDB obviously has the cyclic bond intact. (I am
> asking because when I did not use the loadPDBusingseq function while
> simulating the peptide only, despite starting with an intact cyclic
> peptide, the bond did not remain in the simulation)
>
>
> Can someone please help me with this?
>
> Thanks
> Suchetana
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>


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Received on Fri Nov 11 2022 - 02:00:02 PST
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