Why my protein collapses after the MD simulation?

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1

GROMACS version: 2022.5
GROMACS modification: No

I performed a 150 ns MD simulation for DENV NS1 hexamer protein downloaded from PDB. After 150 ns the complex has distorted significantly. why is that? and how can I minimize that?

hex2
hex21366×601 194 KB

This is the mdp file I used for my simulation

; Run parameters
integrator = md ; leap-frog integrator
nsteps = 75000000 ; 2 * 75000000 = 150000 ps (150 ns)
dt = 0.002 ; 2 fs
; Output control
nstxout = 0 ; suppress bulky .trr file by specifying
nstvout = 0 ; 0 for output frequency of nstxout,
nstfout = 0 ; nstvout, and nstfout
nstenergy = 5000 ; save energies every 10.0 ps
nstlog = 5000 ; update log file every 10.0 ps
nstxout-compressed = 5000 ; save compressed coordinates every 10.0 ps
compressed-x-grps = System ; save the whole system
; Bond parameters
continuation = yes ; Restarting after NPT
constraint_algorithm = lincs ; holonomic constraints
constraints = h-bonds ; bonds involving H are constrained
lincs_iter = 1 ; accuracy of LINCS
lincs_order = 4 ; also related to accuracy
; Neighborsearching
cutoff-scheme = Verlet ; Buffered neighbor searching
ns_type = grid ; search neighboring grid cells
nstlist = 10 ; 20 fs, largely irrelevant with Verlet scheme
rcoulomb = 1.0 ; short-range electrostatic cutoff (in nm)
rvdw = 1.0 ; short-range van der Waals cutoff (in nm)
; Electrostatics
coulombtype = PME ; Particle Mesh Ewald for long-range electrostatics
pme_order = 4 ; cubic interpolation
fourierspacing = 0.16 ; grid spacing for FFT
; Temperature coupling is on
tcoupl = V-rescale ; modified Berendsen thermostat
tc-grps = Protein Non-Protein ; two coupling groups - more accurate
tau_t = 0.1 0.1 ; time constant, in ps
ref_t = 300 300 ; reference temperature, one for each group, in K
; Pressure coupling is on
pcoupl = Parrinello-Rahman ; Pressure coupling on in NPT
pcoupltype = isotropic ; uniform scaling of box vectors
tau_p = 2.0 ; time constant, in ps
ref_p = 1.0 ; reference pressure, in bar
compressibility = 4.5e-5 ; isothermal compressibility of water, bar^-1
; 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

2

If your protein structure collapses or unfolds locally, this usually isn’t a problem with the MD engine or .mdp settings. This might happen if you started from a structure that:

  • is low-resolution
  • misses some binding partners (I guess this would be the case here, as the hexamer is isolated from the capsid)
  • has different solvent conditions than experimentally

etc. etc. In short, the existence of a structure in the PDB does not guarantee that it will remain stable in a simulation (although usually that’s quite likely); often there other biochemical issues to consider.

3

thank you for your comment