[gmx-users] too many lincs warnings

[Justin Lemkul]

On 8/20/14, 3:59 AM, Meenakshi Rajput wrote:
> hello users
> I had done energy minimisation of protein-ligand complex and i got negative
> potential. Also the ligand was at right place after EM run but when I tried
> the positional restrained run, too many lincs warnings came and md run
> stopped suddenly. I am using charmm force field and mdp file settings for
> position restrined run are:-
> define        = -DPOSRES    ; position restrain the protein
> ; Run parameters
> integrator    = md        ; leap-frog integrator
> nsteps        = 50000        ; 2 * 50000 = 100 ps
> dt        = 0.002        ; 2 fs
> ; Output control
> nstxout        = 500        ; save coordinates every 0.2 ps
> nstvout        = 500        ; save velocities every 0.2 ps
> nstenergy    = 500        ; save energies every 0.2 ps
> nstlog        = 500        ; update log file every 0.2 ps
> ; Bond parameters
> continuation    = yes        ; first dynamics run
> constraint_algorithm = lincs    ; holonomic constraints
> constraints    = all-bonds    ; all bonds (even heavy atom-H bonds)
> constrained
> lincs_iter    = 1        ; accuracy of LINCS
> lincs_order    = 4        ; also related to accuracy
> ; Neighborsearching
> cutoff-scheme   = Verlet
> ns_type        = grid        ; search neighboring grid cells
> nstlist        = 10        ; 10 fs
> rlist        = 1.2        ; short-range neighborlist cutoff (in nm)
> rcoulomb    = 1.2        ; short-range electrostatic cutoff (in nm)
> rvdw        = 1.2        ; short-range van der Waals cutoff (in nm)
> rvdw-switch     = 1.0

You need the force-switch method as your vdw-modifier if you are using CHARMM.

> ; 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 off
> pcoupl        = no         ; no pressure coupling in NVT
> ; Periodic boundary conditions
> pbc        = xyz        ; 3-D PBC
> ; Dispersion correction
> DispCorr    = EnerPres    ; account for cut-off vdW scheme
> ; Velocity generation
> gen_vel        = yes        ; assign velocities from Maxwell distribution
> gen_temp    = 300        ; temperature for Maxwell distribution
> gen_seed    = -1        ; generate a random seed
>
> Please tell me if there is something wrong with mdp settings or is it some
> other problem?
>

Usual diagnostics apply:

http://www.gromacs.org/Documentation/Terminology/Blowing_Up#Diagnosing_an_Unstable_System

The ligand is the first place I'd start.  Simplify the system - put the ligand 
in vacuum and run it to see if it is stable, if it is put it in water and run, etc.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================