Dear all,
I am interested in carrying out a simulation to understand the interaction
of a few ligands with a protein.
I had gone across few of the tutorials and could understand that the steps
taken and files used, in order to run a simulation vary depending on the
endgoal. In brief, there are three different ways of analyzing the
protein-ligand interaction.
1) LIE
2) WAMM
3) MM PBSA/MM GBSA.
In addition to that, we would have to carry out one trajectory (only
complex) or three trajectory analysis (protein, ligand and complex),
depending on the endgoal.
I would like to analyze the protein - ligand interaction using the MM PBSA
method. I need help as I am confused as to what my min.in, heat.in, press.in,
eq.in and md.in should be.
In the tutorials it is mentioned that the nstlim steps need to achieve a
relevant result should be more. But there is no mention as to how many
steps are necessary.
It would be of a huge help if you can point me, in the right direction.
Either by, referring a tutorial or a publication.
I was able to create the files necessary for simulation using the following
steps. Could you please go through the same and let me know, if i am on the
right track.
Steps for running MD protein - ligand simulation in Amber
1) Preparation of Protein and Ligand
-Use Chimera to remove hydrogens and save both in amber format as
protein_noh.pdb & lig_noh.pdb
-Protein prep:
a) Upload protien_noh.pdb to H++ and go with default settings.
b) save the .crd and .top files as pro.crd and pro.top for later
c) combine files to form protein
ambpdb -p pro.top -c pro.crd > pro.pdb
d) c) check for change in number of residues (they will be less)
- Ligand prep:
a) Add hydrogens using Chimera and save resultant structure as lig.pdb
b) Use Antechamber to create mol2 file with charge as well as atoms renamed
$ antechamber -i lig.pdb -fi pdb -o LIG.mol2 -fo mol2 -c bcc -nc 0 -s 2
$ parmchk -i LIG.mol2 -f mol2 -o LIG.frcmod
Transfer necessary files to folder named "tleap"
--
tleap_lig.in (contents) <http://tleap_lig.in>
source /home/cosmos10/Prasanth/amber16/dat/leap/cmd/oldff/leaprc.ff99SB
source leaprc.gaff
LIG = loadmol2 LIG.mol2
check LIG
loadamberparams LIG.frcmod
saveoff LIG LIG.lib
saveamberparm LIG LIG.prmtop LIG.inpcrd
savepdb LIG LIG.pdb
quit
--
$ tleap -f tleap_lig.in <http://tleap2.in> > tleap_lig.out
tleap2 (contents)
--
source /home/cosmos10/Prasanth/amber16/dat/leap/cmd/oldff/leaprc.ff99SB
loadamberparams frcmod.ionsjc_tip3p
source leaprc.gaff
set default PBRadii mbondi2
PRO = loadpdb pro.pdb
bond PRO.4.SG PRO.15.SG
bond PRO.5.SG PRO.128.SG
bond PRO.9.SG PRO.25.SG
bond PRO.27.SG PRO.37.SG
bond PRO.538.SG PRO.544.SG
charge PRO
addIons2 PRO Cl- 0
check PRO
saveoff PRO PRO.lib
LIG = loadmol2 LIG.mol2
loadamberparams LIG.frcmod
check LIG
saveoff LIG LIG.lib
COM = combine {PRO LIG}
check COM
charge COM
saveamberparm COM Com_gas.prmtop Com_gas.inpcrd
saveAmberParm PRO Pro_gas.top Pro_gas.crd
saveAmberParm LIG Lig_gas.top Lig_gas.crd
saveoff COM COM.lib
savepdb COM Com_gas.pdb
savepdb PRO Pro_gas.pdb
savepdb LIG LIG_gas.pdb
solvateBox COM TIP3PBOX 12.0
saveAmberParm COM COM_solvated.top COM_solvated.crd
solvateBox PRO TIP3PBOX 12.0
saveAmberParm PRO Pro_solvated.top Pro_solvated.crd
solvateBox LIG TIP3PBOX 12.0
saveAmberParm LIG Lig_solvated.top Lig_solvated.crd
savepdb COM Com_solvated.pdb
savepdb PRO Pro_solvated.pdb
savepdb LIG Lig_solvated.pdb
quit
--
$ tleap -f tleap2.in > tleap2.out
----
One more query here, Do we need to add the ions (for neutralizing) to the
Complex or the protein itself.
Thank you in advance.
Regards,
Prasanth.
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Received on Wed Mar 06 2019 - 06:00:04 PST
