Hi developers,

 

I'm having difficulty minimizing ribosome structures using real_space_refine. The structures are mostly fine (I think) and there are no sever close-contacts. But it seems to happen in particular with waters and/or hydrogens present. See below for an example error message.

 

Searching the mailing list archive, I found an old thread on the same topic where Pavel explained that this can happen when the weights are set improperly.

 

https://phenix-online.org/pipermail/phenixbb/2017-November/023588.html

 

I suspect my problems are related to the ad hoc method of setting weights does not work well for a large structure with 150,000+ atoms. When I check the log file, the weight estimation looks like this:

 

XYZ refinement

**************

Weight determination summary:

   number of chunks: 2038

   random chunks:

   chunk 1215 optimal weight:   50.0000

   chunk 784 optimal weight:    5.9990

   chunk 1173 optimal weight:   50.0000

   chunk 591 optimal weight:   30.0000

   chunk 385 optimal weight:   50.0000

   chunk 380 optimal weight:    2.9990

   chunk 1248 optimal weight:   50.0000

   chunk 1338 optimal weight:   50.0000

   chunk 971 optimal weight:   50.0000

   chunk 183 optimal weight:   50.0000

   chunk 1543 optimal weight:   50.0000

   overall best weight:   27.7996

 

So there seems to be a large discrepancy for the optimal weight for different chunks. Out of a 10-macro cycle run (crashed on the last cycle), the overall best weight varied between 3.7 and 34, which I suspect contributes to the unstable minimization procedure.

 

   overall best weight:   33.9998

   overall best weight:   20.5996

   overall best weight:    5.0186

   overall best weight:    4.6388

   overall best weight:    3.7586

   overall best weight:   34.1998

   overall best weight:   27.7996

   overall best weight:   18.1996

   overall best weight:    9.1992

 

Do you think a constant weight could be a solution to this problem? Is it possible to set it manually? Which of the weights are set using the heuristic method? Are there different weights for e.g. bonded restraints and "extra" metal bond restraints? There are some references to weights in the .eff file and nonbonded_weight seems to be an interesting option with a default value of 100.

 

Regards,

Daniel

 

 

 

Example run that explodes:

 

phenix.real_space_refine resolution=2 run=minimization_global nproc=4 output.prefix=phe output.suffix=_min ignore_symmetry_conflicts=True  macro_cycles=10 ligands.cif elbow.edits coot-42.pdb map.mrc

 

Traceback (most recent call last):

  File "/Applications/phenix-1.20.1-4487/build/../modules/phenix/phenix/command_line/real_space_refine.py", line 8, in <module>

    run_program(real_space_refine.Program)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/iotbx/cli_parser.py", line 79, in run_program

    task.run()

  File "/Applications/phenix-1.20.1-4487/modules/phenix/phenix/programs/real_space_refine.py", line 207, in run

    log                   = self.logger)

  File "/Applications/phenix-1.20.1-4487/modules/phenix/phenix/refinement/macro_cycle_real_space.py", line 297, in __init__

    self.caller(self.refine_xyz)

  File "/Applications/phenix-1.20.1-4487/modules/phenix/phenix/refinement/macro_cycle_real_space.py", line 312, in caller

    func()

  File "/Applications/phenix-1.20.1-4487/modules/phenix/phenix/refinement/macro_cycle_real_space.py", line 653, in refine_xyz

    self.minimization_no_ncs()

  File "/Applications/phenix-1.20.1-4487/modules/phenix/phenix/refinement/macro_cycle_real_space.py", line 716, in minimization_no_ncs

    log                         = self.log)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/mmtbx/refinement/real_space/individual_sites.py", line 51, in __init__

    gradients_method            = gradients_method)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/mmtbx/refinement/real_space/weight.py", line 87, in __init__

    rms_angles_limit = rms_angles_limit)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/mmtbx/refinement/real_space/individual_sites.py", line 368, in refine

    rms_angles_limit = rms_angles_limit)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/mmtbx/refinement/real_space/individual_sites.py", line 235, in __init__

    weight     = weight)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/mmtbx/refinement/real_space/individual_sites.py", line 112, in refine

    states_collector                = self.states_accumulator)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/cctbx/maptbx/real_space_refinement_simple.py", line 174, in __init__

    exception_handling_params=lbfgs_exception_handling_params)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/scitbx/lbfgs/__init__.py", line 278, in run

    line_search)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/scitbx/lbfgs/__init__.py", line 131, in run_c_plus_plus

    f, g = target_evaluator.compute_functional_and_gradients()

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/cctbx/maptbx/real_space_refinement_simple.py", line 245, in compute_functional_and_gradients

    compute_gradients=True)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/cctbx/geometry_restraints/manager.py", line 1479, in energies_sites

    flags=flags, sites_cart=sites_cart, site_labels=site_labels)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/cctbx/geometry_restraints/manager.py", line 1381, in pair_proxies

    check_bonded_distance_cutoff(sites_frac=sites_frac)

  File "/Applications/phenix-1.20.1-4487/modules/cctbx_project/cctbx/geometry_restraints/manager.py", line 1262, in check_bonded_distance_cutoff

    raise RuntimeError(msg)

RuntimeError: Bond distance > max_reasonable_bond_distance: 58.8204 > 50:

  distance: 19 - 25:  20.675

  distance: 21 - 22:   4.594

  distance: 21 - 23:  14.720

  distance: 22 - 24:  27.218

  distance: 25 - 26:  15.535

  distance: 25 - 138:  20.583

  distance: 26 - 27:  10.976

  distance: 26 - 29:   9.260

  distance: 27 - 28:   6.472

  distance: 27 - 34:  28.251

  distance: 28 - 135:  26.553

  distance: 29 - 30:  30.275

  distance: 30 - 31:  45.594

  distance: 31 - 32:  42.003

  distance: 32 - 33:  58.820

  distance: 34 - 35:  15.118

  distance: 34 - 40:  32.473

  distance: 35 - 36:  10.126

  distance: 35 - 38:  33.272

  distance: 36 - 37:  36.153

  distance: 36 - 41:  14.653

  distance: 38 - 39:  31.110

  distance: 39 - 40:  31.467

  distance: 41 - 42:  36.418

  distance: 42 - 43:  13.145

  distance: 43 - 44:   8.206

  distance: 43 - 45:  40.869

  distance: 45 - 46:  12.390

  distance: 46 - 47:  25.848

  distance: 46 - 49:  16.457

  distance: 47 - 48:  15.264

  distance: 47 - 53:  38.374

  distance: 49 - 50:  27.548

  distance: 50 - 51:  46.020

  distance: 50 - 52:  31.107

  distance: 53 - 54:  25.030

  distance: 54 - 55:  33.266

  distance: 55 - 56:  15.731

  distance: 55 - 57:  17.553

  distance: 57 - 58:   8.147

  distance: 58 - 59:  15.533

  distance: 58 - 61:   3.968

  distance: 59 - 60:  32.012

  distance: 59 - 66:  13.102

  distance: 60 - 143:  27.836

  distance: 61 - 62:  21.904

  distance: 62 - 63:  22.068

  distance: 63 - 64:  40.044

  distance: 64 - 65:  14.241

  distance: 66 - 67:  13.162

  distance: 67 - 68:  14.727

  distance: 67 - 70:  18.482

  distance: 68 - 69:   7.119

  distance: 68 - 74:  16.874

  distance: 70 - 71:  23.617

  distance: 70 - 72:  26.751

  distance: 71 - 73:  31.237

  distance: 74 - 75:  24.016

  distance: 74 - 146:  23.850

  distance: 75 - 76:  10.199

  distance: 75 - 78:  26.004

  distance: 76 - 77:  12.111

  distance: 76 - 81:  13.195

  distance: 77 - 157:  10.604

  distance: 78 - 79:  24.115

  distance: 78 - 80:  26.622

  distance: 81 - 82:   9.528

  distance: 82 - 83:  10.254

  distance: 82 - 85:   9.660