[gmx-users] energy minimisation - LINCS WARNING

[Justin Lemkul]

Please don't reply to digests or unrelated threads when starting a new topic; it 
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On 10/2/16 6:11 PM, Nash, Anthony wrote:
> Hi all,
>
> I had a homology/de-novo model .pdb converted into .gro, solvated,
> neutralised and now I¹m going through a series of energy minimisation
> steps. Unfortunately, during energy minimisation I get LINCS WARNINGS
> (angle relative constraint deviation). The the naked eye, the atoms
> involved don¹t look untoward.
>
>
> When I used LINCS all-bond I get the following error:
> -----------------------------------
>
> Step -1, time -0.001 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.001657, max 0.033500 (between atoms 1362 and 1363)
> bonds that rotated more than 30 degrees:
>  atom 1 atom 2  angle  previous, current, constraint length
>
>
>
> When I reduced this to only be the hydrogen bonds (h-bonds) I get:
> -----------------------------------
> Step 20, time 0.02 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.000000, max 0.000000 (between atoms 1322 and 1324)
> bonds that rotated more than 30 degrees:
>  atom 1 atom 2  angle  previous, current, constraint length
>    1360   1361   37.5    0.1010   0.1010      0.1010
> [continues with more errors until Segmentation fault 11]
>
>
> I have tried both constraints with a reduced and increased deltaStep
> (0.2,0.02,0.002,0.0002) no change. I have also taken constraints off, this
> does work but then fails again when constraints are returned. I have tried
> both Steep and cg, both fail with the same result.
>
> The .mdp file I used (taken from the latest release of Justin¹s tutorials)
> is:
> ; energy.mdp - used as input into grompp to generate em.tpr
> ; Parameters describing what to do, when to stop and what to save
> integrator      = steep         ; Algorithm (steep = steepest descent
> minimization)
> emtol           = 700.0        ; Stop minimization when the maximum force
> < 1000.0 kJ/mol/nm
> emstep          = 0.002          ; Energy step size
> nsteps          = 200000                ; Maximum number of (minimization)
> steps to perform
>
> ; Parameters describing how to find the neighbors of each atom and how to
> calculate the interactions
> cutoff_scheme = verlet
> nstlist         = 20            ; Frequency to update the neighbor list
> and long range forces
> ns_type         = grid          ; Method to determine neighbor list
> (simple, grid)
> rlist           = 1.4           ; Cut-off for making neighbor list (short
> range forces)
> coulombtype     = PME           ; Treatment of long range electrostatic
> interactions
> rcoulomb        = 1.4           ; Short-range electrostatic cut-off
> rvdw            = 1.4           ; Short-range Van der Waals cut-off
> pbc             = xyz           ; Periodic Boundary Conditions (yes/no)
>
> ;ADDED THIS BIT MYSELF
> continuation    = no               ; first dynamics run
> constraint_algorithm = lincs    ; holonomic constraints
> constraints     = h-bonds; all-bonds (even heavy atom-H bonds) constrained
> lincs_iter      = 1                         ; accuracy of LINCS
> lincs_order     = 8                         ; also related to accuracy
>
>
> The .pdb was generated using I-TASSER. I have tried refining the hydrogen
> placement via -ignh during pdb2gmx, and I also tried ³Protein Preparation²
> (bond ordering - again, hydrogen bond placement) in Schrodinger. All the
> same.
>
> I was hoping that I could actually watch a rough-and-ready minimisation
> using Avogadro, however, the release I have keeps crashing whilst trying
> to open large structures.
>
> Any suggestions on what I could try next?
>

All signs point to unreasonable starting structure.  How about minimizing the 
protein alone, in vacuo?  Maybe restrain the backbone and try to minimize side 
chains, then in the absence of any restraints?

-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

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

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