[gmx-users] protein-protein simulation

[Mark Abraham]

On 9/01/2012 10:35 PM, Guido Leoni wrote:
> Dear List
> I'm newbie to MD .
> I'd like to simulate a protein protein binding dinamic between 2 
> proteins of 500 aa each one. I have some very basic questions:
> 1) In order to setup my dinamic i'm following the basic tutorial on 
> spider toxin peptide 
> (http://www.gromacs.org/Documentation/Tutorials#Protein-Ligand_Systems) starting 
> from a pdb with the 2 structures near each other and oriented 
> according to some docking calculations. Is this procedure a reasonable 
> starting point?

I guess so. It tests only that orientation, of course. Using the pull 
code to measure the free energy of (un)binding might be fruitful, but do 
read the literature here.

>
> 2)  I tryed to run the MD with the same  parameters of tutorial in my 
> md.mdp file (listed at the end of the mail). Should i set the 
> contraints parameter to "none"? In order to allow more flexibility of 
> the side  chains?
> Finally if the previous points are reasonable ...

Constraints pertain to individual bonds and angles. Not using them 
requires a larger integration time step. While it's conceivable that 
some extra flexibility at bond-and-angle level in the bound 
configuration might affect the binding energy a little, the error in 
that quantity is likely to be limited by the fixed-point-charge 
approximation. A suitable point charge for a near-surface atom when 
bound would differ from that when unbound. So you may as well have 
constraints and virtual sites and have a large time step.

> 3) In your opinion which could be a reasonable time to explore the 
> possibility that the 2 proteins bind each other? I'm  making some 
> attempts using 500 ps for now

Off the cuff, I'd think that at least an order of magnitude too low, but 
you should check out the existing literature for similar work.

>
> Sorry for my silly questions and thank you very much for any kind of help
> Best
> Guido
> define              =  -DPOSRES

Position restraints will prevent relative COM motion.

Mark

> constraints         =  all-bonds
> integrator          =  md
> dt                  =  0.002 ; ps !
> nsteps              =  50000 ; total 100.0 ps.
> nstcomm             =  10
> nstxout             =  500 ; collect data every 1.0 ps
> nstxtcout           =  500
> nstvout             =  5000
> nstfout             =  0
> nstlog              =  10
> nstenergy           =  50
> nstlist             =  10
> ns_type             =  grid
> rlist               =  1.0
> coulombtype  =  PME
> rcoulomb            =  1.0
> vdwtype             =  cut-off
> rvdw                =  1.4
> pme_order  =  4
> ewald_rtol =  1e-5
> optimize_fft =  yes
> DispCorr = no
> ; Berendsen temperature coupling is on
> Tcoupl              =  v-rescale
> tau_t               =  0.1 0.1
> tc-grps  =  protein non-protein
> ref_t               =  300 300
> ; Pressure coupling is off
> Pcoupl              =  no
> Pcoupltype          =  isotropic
> tau_p               =  1.0
> compressibility     =  4.5e-5
>
>
> -- 
> Guido Leoni
> National Research Institute on Food and Nutrition
> (I.N.R.A.N.)
> via Ardeatina 546
> 00178 Rome
> Italy
>
> tel     + 39 06 51 49 41 (operator)
>         + 39 06 51 49 4498 (direct)
>
>

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