[gmx-users] Bond constraints during the equilibration for membrane-protein system

[Justin A. Lemkul]

li lv wrote:
> Dear Justin
> 
>  
> 
> Thanks for your reply. Generally I conduct the simulation following the 
> tutorial on your website. The system contains an integrin alpha2b/beta3 
> transmembrane portion (PDB 2KNC) embedding in a 124-lipids DPPC bilayer 
> and solvated in water. The initial membrane-protein system is built with 
> INFLATEGRO. Here is the topology file of the system (not completed):
> 
> “
> 
> ; Include forcefield parameters
> 
> #include "ffG53a6_lipid.itp"
> 
>  
> 
> ; Include chain topologies
> 
> #include "topol_A.itp"
> 
>  
> 
> ; Include Position restraint file
> 
> #ifdef POSRES
> 
> #include "posre_A.itp"
> 
> #endif
> 
>  
> 
> #include "topol_B.itp"
> 
>  
> 
> ; Include Position restraint file
> 
> #ifdef POSRES
> 
> #include "posre_B.itp"
> 
> #endif
> 
>  
> 
> ; Include DPPC chain topology
> 
> #include "dppc.itp"
> 
>  
> 
> ; Include water topology
> 
> #include "spc.itp"
> 
>  
> 
> #ifdef POSRES_WATER
> 
> ; Position restraint for each water oxygen
> 
> [ position_restraints ]
> 
> ;  i funct       fcx        fcy        fcz
> 
>    1    1       1000       1000       1000
> 
> #endif
> 
>  
> 
> ; Include generic topology for ions
> 
> #include "ions.itp"
> 
>  
> 
> [ system ]
> 
> ; Name
> 
> Protein in water
> 
>  
> 
> [ molecules ]
> 
> ; Compound        #mols
> 
> Protein_A           1
> 
> Protein_B           1
> 
> DPPC 124
> 
> SOL             17185
> 
> NA+ 2
> 
> ”
> 
>  
> 
> For the details of energy minimization, here is one of the mdp files for 
> energy minimization:
> 
> “
> 
> define = -DPOSRES
> 
> integrator = cg
> 
> emtol = 500.0      
> 
> emstep = 0.01   
> 
> nstcgsteep = 100
> 
> nsteps     = 50000 
> 
>  
> 
> nstlist = 1      
> 
> ns_type = grid
> 
> rlist = 1.2             
> 
> coulombtype = PME            
> 
> rcoulomb = 1.2            
> 
> rvdw = 1.2           
> 
> pbc = xyz
> 
>  
> 
>  
> 
> freezegrps = Protein-H
> 
> freezedim = Y Y Y  
> 
> ”
> 
> As you may notice, I froze the heavy atoms of the protein during the 
> first energy minimization and then in the following the EMs the frozen 
> group was MainChain, C-alpha and none in order. The system finally 
> reached Fmax < 500.
> 

But do you maintain position restraints?  Restraints during minimization serve 
little use, and they actually are probably preventing some necessary structural 
changes from happening.  I'd suspect that's the reason for your instability - 
you're not minimizing as well as your system requires.

I would also say that there is no point in using both freezegrps and position 
restraints during equilibration, especially NPT, where freezegrps actually 
interfere with proper coordinate scaling.  I would suggest you simply use 
position restraints.

-Justin

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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