[gmx-users] issues running virus capsid simulation

[David van der Spoel]

Den 2019-09-25 kl. 02:37, skrev Justin Lemkul:
> 
> 
> On 9/24/19 5:09 PM, Asis Jana wrote:
>> Hi,
>>
>> I am doing viral capsid simulation using GROMACS 2018. The capsid was 
>> first
>> energy minimized using the steepest-descent algorithm followed by 40 
>> ns of
>> NVT (300 K) followed by 10 ns of NPT (300 K, 1 atm) equilibration. In the
>> NVT and NPT equilibration, the heavy atoms of the protein were restrained
>> with a force constant of 1000 kJ/mol/nm. Production MD simulations were
>> performed for 400 ns at a temperature of 300 K and a pressure of 1 atm.
>> Please see the production mdp file below.
>>
>> title           = MD simulation
>> ; Run parameters
>> integrator      = md
>> nsteps          = 2000000000
>> dt                  = 0.002
>> ; Output control
>> nstxout                 = 50000
>> nstvout                 = 50000
>> nstenergy               = 50000
>> nstlog                  = 50000
>> nstxout-compressed  = 50000
>>
>> compressed-x-grps   = System
>>
>> continuation            = yes
>> constraint_algorithm    = lincs
>> constraints                 = h-bonds
>> lincs_iter                  = 1
>> lincs_order                 = 4
>> ; Neighborsearching
>> cutoff-scheme   = Verlet
>> ns_type             = grid
>> nstlist                 = 20
>> rlist                   = 1.2
>> coulombtype             = pme
>> rcoulomb                = 1.2
>> vdwtype                 = Cut-off
>> vdw-modifier            = Force-switch
>> rvdw_switch             = 1.0
>> rvdw                    = 1.2
>> pme_order           = 4
>> fourierspacing  = 0.16
>> ; Temperature coupling is on
>> tcoupl          = Nose-Hoover
>> tc-grps         = Protein Non-Protein
>> tau_t           = 1.0     1.0
>> ref_t           = 300     300
>> ; Pressure coupling is on
>> pcoupl                  = Parrinello-Rahman
>> pcoupltype              = isotropic
>> tau_p                   = 5.0
>> ref_p                   = 1.0
>> compressibility     = 4.5e-5
>> refcoord_scaling    = com
>> ; Periodic boundary conditions
>> pbc             = xyz           ; 3-D PBC
>> ; Dispersion correction
>> DispCorr        = EnerPres      ; account for cut-off vdW scheme
>> ; Velocity generation
>> gen_vel         = no            ; Velocity generation is off
>> nstcomm                 = 100
>> comm_mode               = linear
>> comm_grps               = Protein Non-Protein
>>
>> I have attached RMSD and Rg plots with this mail. It looks like that 
>> capsid
>> is stiil not equilibrated. Rg is increasing rapidly, whereas RMSD of the
>> capsid is increasing slowly. Please see the attached plots.  Any kind of
>> advice or suggestions are deeply appreciated.
> 
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> 
> What do your eyes tell you when you visualize the trajectory? Do the 
> data make sense? Have you accounted for periodicity effects? Are there 
> simply structural changes happening? Nothing says any structural metric 
> has to level off in some convenient amount of time.
> 

Indeed, big things take long time to equilibrate. For a virus it may 
depend on whether a genome is present, ions etc. We did this stuff8 
years ago and it take many microseconds:

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002502

https://pubs.acs.org/doi/abs/10.1021/ct3002128

> -Justin
> 


-- 
David van der Spoel, Ph.D., Professor of Biology
Head of Department, Cell & Molecular Biology, Uppsala University.
Box 596, SE-75124 Uppsala, Sweden. Phone: +46184714205.
http://www.icm.uu.se