[GaMD-discuss] Question about proper sigma0P value

[Li, J. <JO...@pi...>]

Hello,

I am trying to use LiGAMD3 for measuring the binding kinetics between protein and ligand. The system I use is PDB 5JID. The original system has two ligands, but I kept only one for the GAMD. I followed the discussions in paper (10.1021/acs.jctc.4c00502) and tried to find the right sigma0p for unbinding the ligand. But even if I set the sigma0P to 8, the ligand still binds with the protein and the ligand RMSD is lower than 2 A after 100 ns production run. Attached are the codes for the simulation (pasted below as well) and the log file for the 100 ns production when P is 8.  Did I do something wrong, or should I go for an even much higher P value? I have been trying this for months but not seenthe ligand to move. So I will appreciate any suggestions!

Thank you,

Best,
Qianwei

equbrilium
cMD and GaMD equilbrium
 &cntrl
   ig = -1,             ! Pseudo-random number generator (random seed based on time)
   ntx = 1,             ! no initial coordinates and velocity(ASCII)
   imin = 0,            ! Minimization (No)
   irest = 0,           ! Restart the Simulation? (no) use previous velocity
   cut = 8,            ! Non-bonding Cut-off (8 A)
   ntc = 2,             ! SHAKE bond length constraints (constrain bonds with H)
   ntf = 1,             ! compelete interaction is calculated
   tol = 0.000001,   !relatve geometrical tolerance in shake
   dt = 0.002,                      ! timestep = 2fs
   iwrap = 1,            !set for long runs to keep coordinate from overflowing
   nstlim = 44000000,     ! Simulation length (sum of ntcmd and nteb total 88 ns)
   ntb = 2,                         ! PBC (Constant pressure)
   ntp = 1,                             ! isotropic position scaling
   barostat = 1,                         ! for control pressure, Berendsen
   ntt = 3,                   ! Temperature scaling (Stochastic version of Berendsen thermostat)
   gamma_ln=5.0,
   temp0 = 300,               ! Reference temperature (300K, physiological temperature)
   tempi = 300.0,                 !Initial temperature
   ntpr = 500000,         ! Energy save interval (every 500000 steps or 1 ns)
   ntwx = 500000,         ! Coordinate/trajectory save interval (every 500000 steps or 1 ns)
   ntwprt = 7101,      !number of atoms to be saved
   ntwr = 5000000,    ! Write restart file every 10 ns
   igamd = 28,
   iE = 2,                     !thershold energy to the lower bound
   irest_gamd = 0,       !not a restart gamd
   ntcmd = 4000000,    !8 ns cMD
   nteb = 40000000,     !80 ns GAMD
   ntave = 400000,        !four times total number of atoms
   ntcmdprep = 800000,   !1.6 ns number of cMD not collected for statistics calculation
   ntebprep = 800000,   !1.6 ns GAMD for preperation
   sigma0P = 8.0,
   sigma0D = 6.0,
   sigma0B = 6.0,
   iEP=2, iED=2, iEB=1,
   bgpro2atm=1,
   edpro2atm=7076,
   gti_cpu_output=0,
   gti_add_sc=1,
   icfe = 1,
   ifsc = 1,
   timask1=':7077-7101',
   scmask1=':7077-7101',
   timask2='',
   scmask2='',
 &end
END

production
GaMD production
 &cntrl
   ig = -1,             ! Pseudo-random number generator (random seed based on time)
   ntx = 1,             ! no initial coordinates and velocity(ASCII)
   imin = 0,            ! Minimization (No)
   irest = 0,           ! Restart the Simulation? (no) use previous velocity
   cut = 8,            ! Non-bonding Cut-off (8 A)
   ntc = 2,             ! SHAKE bond length constraints (constrain bonds with H)
   ntf = 1,             ! compelete interaction is calculated
   tol = 0.000001,   !relatve geometrical tolerance in shake
   dt = 0.002,                      ! timestep = 2fs
   iwrap = 1,            !set for long runs to keep coordinate from overflowing
   nstlim = 50000000,     ! Simulation length (sum of ntcmd and nteb total 100 ns)
   ntb = 2,                         ! PBC (Constant pressure)
   ntp = 1,                             ! isotropic position scaling
   barostat = 1,                         ! for control pressure, Berendsen
   ntt = 3,                   ! Temperature scaling (Stochastic version of Berendsen thermostat)
   gamma_ln=5.0,
   temp0 = 300,               ! Reference temperature (300K, physiological temperature)
   tempi = 300.0,                 !Initial temperature
   ntpr = 250000,         ! Energy save interval (every 250000 steps or 500ps)
   ntwx = 500,         ! Coordinate/trajectory save interval (every 500 steps or 1ps)
   ntwprt = 7101,      !number of atoms to be saved
   ntwr = 5000000,    ! Write restart file every 10 ns
   igamd = 28,
   iE = 2,                       !thershold energy to the lower bound
   irest_gamd = 1,       !a restart gamd
   ntcmd = 0,    !no cMD
   nteb = 0,     !0 GAMD
   ntave = 400000,        !four times total number of atoms
   ntcmdprep = 0,   !no cMD preperation
   ntebprep = 0,   !noGAMD for preperation
   sigma0P = 8.0,
   sigma0D = 6.0,
   sigma0B = 6.0,
   iEP=2, iED=2, iEB=1,
   bgpro2atm=1,
   edpro2atm=7076,
   gti_cpu_output=0,
   gti_add_sc=1,
   icfe = 1,
   ifsc = 1,
   timask1=':7077-7101',
   scmask1=':7077-7101',
   timask2='',
   scmask2='',
 &end
END