[gmx-users] Vacuum simulations

[Martina Bertsch, PhD]

Greetings.

I would like to refine Autodock3 results of docking a nonpeptidic 
indolic ligand to a membrane receptor model. Because it is 
computationally expensive to simulate receptors in the membrane (the 
5-ns position restrained MD to relax the POPC takes me ~ 20 days), I 
would like to use MD or simulated annealing in vacuum for some 
intermediate refinement steps.

I can generate the protein gro file suitable for vacuum simulations by 
selecting the ffG43b1 parameter set in pdb2gmx. But, how do I generate 
the ligand gro and itp consistent with this forcefield? I tried using 
the ffgmx version of the ligand (as created in PRODRG) and editing the 
vacuum ff to include the atomtypes, but somehow that does not seem like 
the right thing to do.

Enclosed are my md.mdp and sa.mdp for the vacuum MD and SA of the 
receptor-ligand complex, respectively, with position restraints on the 
transmembrane (TM) C-alpha atoms. Are the parameters appropriate for 
vacuum simulations, in particular the coulombtype, rcoulomb, vdwtype, 
rvdw, rlist and the temperature coupling groups?

Which energy groups do I specify for monitoring to estimate the 
receptor-ligand binding energy: protein and drg or protein_drg?

 I appreciate your input.

Martina Bertsch, Ph.D.

md.mdp

title                 =  Rec-Lig MD
cpp                 =  /lib/cpp
define              =  POSRE_TM
constraints       =  all-bonds
integrator         =  md
dt                    =  0.001    ; ps !
nsteps              =  2000000 ; total 2 ns.
;nstcomm         =  1
nstxout             =  50000
nstvout             =  50000
nstfout              =  50000
nstlog               =  50000
nstenergy         =  50000
nstxtcout          =  50000
nstlist               =  10
ns_type           =  grid
rlist                  =  1.0
coulombtype    =  cut-off
rcoulomb         =  1.4
epsilon_r         =  4
vdwtype          =  cut-off
rvdw               =  1.4
pbc                 =  no
comm_mode   =  linear
nstcomm         =  1
comm_grps      =  system       ; protein_drg
; Berendsen temperature coupling is on in two groups
Tcoupl              =  berendsen
tau_t                 =  0.1      0.1
tc-grps              =  protein  drg
ref_t                  =  300      300
; Energy monitoring
energygrps         =  system      ; protein_drg
; Pressure coupling is on
Pcoupl               =  no
pcoupltype         =  isotropic
tau_p                 =  5  
compressibility   =  4.5e-5  
ref_p                 =  1.0
; Generate velocites is on at 300 K.
gen_vel              =  yes
gen_temp           =  300.0
gen_seed            =  031775


sa.mdp

title                   =  Rec-Lig SA
cpp                  =  /lib/cpp
define               = POSRE_TM
constraints        =  all-bonds
integrator          =  md
dt                     =  0.001   ; ps !
nsteps              =  1000000   ; total 1 ns.
;nstcomm         =  1
nstxout             =  5000
nstvout             =  5000
nstfout              =  5000
nstlog               =  5000
nstenergy          =  5000
nstxtcout           =  5000
nstlist                =  10
ns_type             =  grid
rlist                   =  1.0
coulombtype     =  cut-off
rcoulomb          =  1.4
epsilon_r          =  4
vdwtype           =  cut-off
rvdw                =  1.4
pbc                  =  no
comm_mode    =  linear
nstcomm          =  1
comm_grps      =  protein_drg
; Berendsen temperature coupling is on in three groups
Tcoupl             =  berendsen
tau_t                =  0.1      0.1
tc-grps             =  protein  drg
ref_t                 =  600      600
; Energy monitoring
energygrps       =  protein  drg
; Pressure coupling is on
Pcoupl                =  no
pcoupltype          =  isotropic
tau_p                   =  5  
compressibility      =  4.5e-5  
ref_p                    =  1.0   
; Simulated annealing
annealing                =  yes
zero_temp_time      =  1000 ; ps
; Generate velocites is on at 900 K.
gen_vel             =  yes
gen_temp          =  600.0
gen_seed           =  031775