From: Bassam Haddad (bhaddad_at_pdx.edu)
Date: Wed May 11 2022 - 14:42:25 CDT
Hi Christos,
Did you align the protein prior to calculating the rmsd?
Bassam
On Wed, May 11, 2022 at 9:35 PM Efthymiou, Christos <
christos.dereschuk.20_at_ucl.ac.uk> wrote:
> Hello,
>
> I am using QwikMD/NAMD to prepare the molecular dynamics simulation files
> to run a simulation on a supercomputer. The system I am simulating contains
> two protein chains that bind to one another.
>
> I would like to recreate the simulation conditions found in a paper shown
> here:
>
> *"For each site of interaction on X with Y, three explicit solvent MD
> simulations were performed using NAMD and the CHARMM27 force field.
> Structures were initially minimized with the water molecules contained in
> the crystallographic structure and subsequently solvated in a cubic TIP3P
> water box leaving a minimum margin of 12 Å around the protein structure.
> Sodium and chloride ions were also added to the water box, bringing the
> ionic strength to 150 mM. Minimization of the solvated structure was
> performed for 25,000 steps (50 ps) before heating to 310 K over 64 ps.
> Next, equilibration was performed where all protein atoms were constrained
> at 10 kcal/mol/Å2 initially and then relaxed to 5, 2, and 1 kcal/mol/Å2
> before removing constraints altogether for the final equilibration run.
> Following equilibration, the MD simulation was run with periodic boundary
> conditions, Langevin temperature and pressure control, and particle mesh
> Ewald (PME) electrostatics. Relevant parameters for the simulation included
> a nonbonded interaction cutoff of 12 Å and a switching distance of 10 Å.
> Hydrogen bonds were held constant according to the SHAKE algorithm as an
> integration time step of 2 fs was used."*
>
> To recreate the above, I used QwikMD with the following Protocol:
>
> - Minimization - 25000 steps, backbone restraint, NpT, 0 Temp, 1
> Pressure
> - Annealing - 35000 steps, backbone restraint, NpT, 37 Temp, 1
> Pressure
> - Equilibration - 50000 steps, protein restraint, NpT, 37 Temp, 1
> Pressure
> - Equilibration.1 - 50000 steps, protein restraint, NpT, 37 Temp, 1
> Pressure
> - Equilibration.2 - 50000 steps, protein restraint, NpT, 37 Temp, 1
> Pressure
> - Equilibration.3 - 50000 steps, protein restraint, NpT, 37 Temp, 1
> Pressure
> - Equilibration.4 - 50000 steps, no restraint, NpT, 37 Temp, 1 Pressure
> - MD - 500000 steps, no restraint, NpT, 37 Temp, 1 Pressure
>
> I then edited the .conf files with Notepad++ for the equilibration steps
> to make constraintscaling 10 for Equilibration.conf, constraintscaling 5
> for Equilibration.1.conf, etc. to mimic the 10 kcal/mol/Å2, 5, 2, etc.
> constraints from the paper above. Is this the best way to do this? Or is
> there another way? Additionally, I am not sure how to hold the Hydrogen
> bonds constant according to the SHAKE algorithm or if this is done
> automatically.
>
> I then transfer the files to the supercomputer and run the simulation
> before transferring it back to my computer for analysis. When I plot the
> RMSD for the MD trajectory, I see a very large RSMD value. It jumps from
> around 0 angstroms to nearly 5 angstroms within the first couple hundred
> picoseconds, and continues increasing to over 15 angstroms over the course
> of the 10 ns simulation.
>
> Are there any reasons why the RMSD value is so high? I have tried
> searching online for reasons why an RMSD value would be so high during a
> simulation, and I cannot find any information. I am not sure if I am not
> properly recreating the conditions from the paper above or what parameters
> I can try manipulating to make the RMSD value more reasonable. In the
> paper, the RMSD stayed under 5 angstroms so I am confused as to why my RMSD
> values are so high. I have also tried it several times and the same thing
> happens each time.
>
> I appreciate any help!
>
-- ________________________ *Bassam Haddad, Ph.D.* Adjunct Research Associate Portland State University Portland, OR
This archive was generated by hypermail 2.1.6 : Tue Dec 13 2022 - 14:32:44 CST