On 7/10/17 5:57 PM, farial tavakoli wrote:
Dear gmx-users
I have a problem in equilibration my protein-ligand complex and encountered to
this error after 2 steps of 50000 steps:one or more water molecules can not be
settled. check for bad contacts or reduce the time steps.
so I decided to create a topology for my designed drug (50 atoms) as a ligand to
minimize it in the vacuo in the absence of the protein to check if it minimizes ,
so i tried to change the .itp file obtained from PRODRG to create a .top file, in
this way:I added " ; Include forcefield parameters
#include "gromos43a1.ff/forcefield.itp " above the [ moleculetype ]
directive as a first line , then added [ system ] and [ molecule ] directives under the
ligand, respectively :
23 24 26 27 1 180.0 33.5 2 180.0 33.5 2 ; dih CAS CAR NAQ
CAN
32 27 26 24 1 180.0 33.5 2 180.0 33.5 2 ; dih CAM CAN NAQ
CAR
39 37 36 30 1 180.0 5.9 2 180.0 5.9 2 ; dih SAG CAH CAK
CAP
40 48 49 50 1 180.0 7.1 2 180.0 7.1 2 ; dih CAA CAF OAJ
HAJ
; Ligand position restraints
#ifdef POSRES
#include "posre_DRG.itp"
#endif
; Include water topology
#include "gromos43a1.ff/spc.itp"
[ system ]
; Name
DRG in water
[ molecules ]
; Compound #mols
DRG 1
issued this command:gmx grompp -v -f em.mdp -c DRG.gro -p DRG.top -o
DRG-EM-vacuum.tprgmx mdrun -v -deffnm DRG-EM-vacuum -c DRG-EM-vacuum.gro
and simulation results:
Steepest Descents:
Tolerance (Fmax) = 1.00000e+03
Number of steps = 50000
Step= 0, Dmax= 1.0e-02 nm, Epot= 1.41636e+03 Fmax= 2.81150e+04, atom= 25
Step= 1, Dmax= 1.0e-02 nm, Epot= 1.01416e+03 Fmax= 1.21118e+04, atom= 25
Step= 2, Dmax= 1.2e-02 nm, Epot= 7.87016e+02 Fmax= 4.71639e+03, atom= 25
Step= 3, Dmax= 1.4e-02 nm, Epot= 6.94638e+02 Fmax= 5.88719e+03, atom= 15
Step= 5, Dmax= 8.6e-03 nm, Epot= 6.79808e+02 Fmax= 7.13390e+03, atom= 15
Step= 7, Dmax= 5.2e-03 nm, Epot= 6.29169e+02 Fmax= 1.31714e+03, atom= 25
Step= 8, Dmax= 6.2e-03 nm, Epot= 6.12279e+02 Fmax= 2.91712e+03, atom= 14
Step= 10, Dmax= 3.7e-03 nm, Epot= 6.04849e+02 Fmax= 2.77294e+03, atom= 27
Step= 12, Dmax= 2.2e-03 nm, Epot= 5.86062e+02 Fmax= 9.77798e+02, atom= 24
writing lowest energy coordinates.
Back Off! I just backed up DRG-EM-vacuum.gro to ./#DRG-EM-vacuum.gro.1#
Steepest Descents converged to Fmax < 1000 in 13 steps
Potential Energy = 5.8606232e+02
Maximum force = 9.7779791e+02 on atom 24
Norm of force = 3.8248090e+02
Simulation ended prematurely, no performance report will be written.
here's my em.mdp file:
integrator = steep ; Algorithm (steep = steepest descent
minimization)
emtol = 1000.0 ; Stop minimization when the maximum force <
10.0 kJ/mol
emstep = 0.01 ; Energy step size
nsteps = 50000 ; Maximum number of (minimization) steps to
perform
energygrps = system ; Which energy group(s) to write to disk
; Parameters describing how to find the neighbors of each atom and how to
calculate the interactions
nstlist = 1 ; Frequency to update the neighbor list
and long range forces
cutoff-scheme = Verlet
ns_type = grid ; Method to determine neighbor list (simple,
grid)
rlist = 1.0 ; Cut-off for making neighbor list (short
range forces)
coulombtype = PME ; Treatment of long range electrostatic interactions
rcoulomb = 1.0 ; long range electrostatic cut-off
rvdw = 1.0 ; long range Van der Waals cut-off
pbc = xyz ; Periodic Boundary Conditions
To minimize in vacuo, cutoffs should all be set to zero, no PBC, no PME, simple
neighbor searching and group cutoff scheme.
I just wanted to know if I did correct?In addition after minimization in vacuo
, checked my ligand in pymol and noticed it is disintegrated. Is there anyone
help me how come it is disintegrated ,however i edited the .itp file obtained
from PRODRG ( charges and charg groups)? How can i fix this problem to
equilibrate my complex?
You'll have to define "disintegrated" because bonds can't break or form in
classical molecular mechanical processes, so perhaps PyMOL is just having a hard
time guessing the bonded structure. You have to be judicious in what
modifications you make to the topology. PRODRG topologies require complete
reparametrization of (at least) the charges, but without knowing what you did or
why you did it, there's little to go on here.
-Justin
--
==================================================
Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow
Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201
jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
==================================================
--
Gromacs Users mailing list
* Please search the archive at
http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!
* Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
* For (un)subscribe requests visit
https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a
mail to gmx-users-requ...@gromacs.org.
