ProPrep 1.22.0

Added

• MD Manager: how close the solute comes to its own periodic images, along a
  simulation. Under periodic boundaries where the solute sits in the box means
  nothing; its shortest distance to any atom of any copy of itself does, and
  it changes as the solute tumbles or extends and as the box shrinks under
  constant pressure. It is analysis 23 of the trajectory analysis menu
  ("Periodic image distance") and option 12 of the simulation monitor, where
  it covers the frames written so far by a run that is still going. Any Amber
  box is handled: rectangular, truncated octahedron, or triclinic. Reported:
  the box shape and the range of its edges, the closest approach with its
  frame and the two atoms involved (which says what part of the solute is
  approaching its image), the mean and range, and the frames in which the
  solute is within the nonbonded cutoff of its own image, where it interacts
  directly with itself. That cutoff is the only criterion applied. It is read
  from the run's own output, which echoes what the engine used, or from its
  input; if neither is beside the topology, Amber's default of 8 Å is offered
  and said to be that. The solute can be the protein residues, every molecule
  the topology does not mark as solvent (no list of residue names is used),
  chosen residues, or a mask; in a membrane system choose the protein, since
  the lipids are continuous across the box and always touch their images. The
  distances equal those of cpptraj's minimage, and are found faster: about
  0.2 s a frame for 6,000 atoms, where minimage takes 0.9 s and grows with
  the square of the size.
• Membrane Builder: the build now reports packmol's progress. After
  "Initiating all-together packing" ProPrep used to print nothing until the
  build ended, which for a large system is more than an hour. It followed
  packmol-memgen's log, which goes quiet once packmol starts; the progress is
  in packmol's own log. Each packing phase is now named with its loop budget,
  and each loop gives packmol's objective function, its two violations, the
  time per loop and the most time left. A build that is stopped says where
  packmol stood. Ending "without perfect packing" is reported as what it is,
  packmol-memgen's normal outcome: a protein-free POPC patch ends the same
  way and packmol-memgen keeps packmol's best structure.
• Membrane Builder: a warning, as soon as packmol-memgen reports it, when the
  oriented protein has volume in one leaflet only, that is, when it does not
  cross the membrane as placed. For a transmembrane protein this means the
  orientation failed (stop with Ctrl-C and choose another method); for a
  peripheral protein it is expected, so the build is not stopped.
• Membrane Builder: when ProPrep orients the protein with PPM3 and the protein
  came from a PDB entry that the OPM database holds, the placement is compared
  with OPM's before packing starts. OPM's placements are computed with the
  same method and then curated; in particular, which side of the membrane each
  face of the protein is on comes from the literature, which no calculation on
  a structure can know. The build reports whether the protein is the same way
  up as in OPM (in red if it is not), the angle between the two membrane
  normals, how deep the protein's centre sits in each, and OPM's hydrophobic
  thickness. For 6R2Q: the same way up, 1.1° and 0.4 Å apart. It reports and
  changes nothing: "OPM has no entry", no internet connection, or a structure
  that has been moved since it was loaded are each one grey line, never a
  stopped build. It needs the internet and can be switched off (Protein
  Orientation, option 6). The prepared structure is matched to OPM's file
  through the file it was loaded from, by position, so renumbered and renamed
  residues do not matter.
• Membrane Builder, PACKMOL Settings: a time limit for the build (option 9),
  shown in the review. None by default.
• Structure viewer: every row in the Representations panel has a Zoom
  button that frames that row's selection, annotations from the PDB Filter,
  the Protonation State Analyzer and the Redox Site Detector included. It uses
  the selection as it is typed in the row at that moment, works on a hidden
  row, and glides to the new view. A selection that matches no atom leaves the
  view where it is and marks the button and the selection field in red.

Fixed

• Session logs: the first line of a session file read "version": "1.1" and
  the last block "proprep_version": "1.21.0". The first is the version of the
  file's format, not of ProPrep; under that name it looked like ProPrep's, and
  wrong. The key is now session_format_version. Logs recorded before this
  change replay and rewind as before.
• Structure viewer: turning a representation off left its visibility button
  with nothing to see. The eye was replaced by a dash in a grey almost the
  colour of the row behind it (a contrast of 1.26:1), so the button was still
  there to press and could not be found. Both states are now drawn: an open
  eye in white when the representation is shown, the same eye crossed out in
  amber when it is hidden, so that they differ in shape as well as in colour.
  The button's tooltip says which state it is in and what a click will do.
• Structure Completeness: the ACE and NME caps it adds were placed at a fixed
  offset along the x axis of the file, whichever way the residue faced: ACE
  from the residue's first atom, NME from its last, which is usually a
  side-chain atom and not the carbonyl carbon. tLEaP does not correct this: it
  builds only atoms that are missing, and the caps' atoms are given. On a
  repaired 6R2Q the three ACE caps had C-N-CA angles of 166°, 54° and 50° where
  a peptide has 121.7°, and one carbonyl oxygen sat 0.41 Å from the next
  residue's CB. A cap is now built as what it is, a trans peptide bond onto
  the residue, from the residue's own backbone atoms and standard peptide bond
  lengths and angles. NME is then fully determined. ACE has one free rotation,
  the residue before it not being there, and is turned to where it stays
  farthest from every other atom. A residue with no usable backbone keeps the
  old placement, and ProPrep says so. Systems prepared earlier are not wrong
  for it, as long as their minimization ran: it starts from a worse geometry
  and recovers.
• Membrane Builder: packmol's progress reached the screen in bursts, one update
  every five or six packing loops (every five minutes on a large system),
  because packmol-memgen writes packmol's log 8 KB at a time. ProPrep now
  starts packmol-memgen so that its logs are written line by line, which
  changes nothing else about it, and the progress is per loop. When several
  loops do arrive together the latest is shown. The time per loop is measured
  from one loop to the next and is not quoted until two have been seen (it
  used to read "0.0 s per loop" at the first). The long all-together phase
  opens by saying what to expect of it: packmol-memgen does not wait for a
  perfect packing, it keeps the best structure packmol reached; the objective
  falls, jumps when packmol moves its worst-placed molecules, and falls again;
  "lowest so far" is the number to watch.
• Membrane Builder: tLEaP, when it saves a system, moves every water to the
  end of it, and the hydrogen pass let it. A structure with crystal waters
  lying between its cofactors (6R2Q after a repair: 10 waters among the hemes)
  therefore came out with every residue after the first water at another
  position in the file. tLEaP addresses residues in bond commands by that
  position, and the Topology Generator's bond directives are written for the
  order of the structure that went in, so in the bilayer they would have named
  the wrong residues ("bond: Argument #2 is of type String", or, worse, a bond
  made to the wrong atom). Whether it happened depended on where the waters
  were: a structure with its waters after the cofactors was unaffected. The
  hydrogen pass now tells tLEaP to keep the order (set default reorder_residues off), and after the build the protein at the head of the
  bilayer file is compared, atom by atom and residue by residue, with the one
  packmol-memgen was given; a build that fails the comparison is not recorded.
  A bilayer built earlier from a structure with waters between its cofactors
  should be rebuilt.
• Structure Completeness, with redox sites imported from a site file: after a
  repair, each heme site's atoms were moved to the new residue numbers but its
  center stayed on the old one (6R2Q: atoms at A:274, center at A:901), and
  nothing was said. The Redox Site Preparer addresses a site by its center, so
  every step on the heme did nothing: the prepared structure kept 20 residues
  named HEC with all of the heme's atoms, HCO held only the His/Cys side
  chains, there was no PRD, and tLEaP later stopped on "Unknown residue: HEC".
  The cause was one character: a heme's center is the centroid of its residue,
  and that case compared insertion codes as text, where a structure read from
  a file has a space and a center read from a site file had nothing, the site
  file not storing it. Sites detected in the same session, and sites whose
  center is an atom (a disulfide), were not affected. Blank insertion codes
  are now treated as the same, the site file stores the insertion code and
  alternate location, and a center that cannot be placed in the repaired
  structure is reported in red with the advice to detect the sites again.
  Structures prepared from imported sites after a repair should be checked for
  leftover HEC (or other untransformed cofactor) residues.
• Redox Site Preparer: a transformation step that names a residue its site
  does not contain is now reported, in red, at any verbosity and for every
  transformer; the site's own residues are listed. Such a step used to do
  nothing and say nothing, and the structure failed later, somewhere else. A
  step whose residue is present but excluded by a name filter (renaming HEM on
  a heme already called HEC) is normal and stays quiet.
• Membrane Builder: when tLEaP failed to add the hydrogens and topology files
  from an EARLIER build were still in the directory, the builder took them for
  the result and built the membrane around the earlier protein. On 6R2Q that
  was the structure from before a repair: without the rebuilt loops and caps,
  and numbered differently from the bond directives, which tLEaP then refused
  with "bond: Argument #2 is of type String". The hydrogen pass now removes
  its earlier output before it runs, and checks what tLEaP wrote against what
  it was given: every heavy atom at the same coordinates, in the residue at
  the same position in the file, which is how the bond directives address
  residues. If not, the build stops and says what differs. A failed pass now
  leads its explanation with the residues tLEaP did not know ("Unknown
  residue: HEC (20 of them)"). A membrane built before this fix in a directory
  that held an earlier build should be rebuilt.
• Redox sites imported from a JSON file: disulfide sites matched no transformer
  in the Redox Site Preparer ("Compatible Transformers: None", "disulfide ✗ Not
  compatible"; in transformer_compatibility_report.txt, "Both centers must
  have is_disulfide_bonded property (expected 2, got 0)"). The site file did
  not hold what detection had learned about each center, so it was lost
  between export and import; sites detected in the same session were not
  affected. Files are now written with that information, and files written
  before are repaired as they are read: a disulfide site's two cysteines get it
  back from the bond the file does record. Do not work around this by giving
  such a site no_transformation: the two cysteines stay CYS and tLEaP later
  stops on "Could not find bond parameter for atom types: SH - S". Restart
  ProPrep and import the sites again.
• Structure Completeness (MODELLER): when MODELLER could not be told which
  residues it was rebuilding, it refined every atom of the structure, without
  saying so, under a line reading "all resolved atoms (including any metal
  sites) are held fixed". Refining everything moves every atom, metal sites
  and their ligands included, and takes the structure off its deposited
  coordinates. The repair now stops and asks first, and the default is to leave
  the structure unchanged. After every MODELLER run ProPrep reports how many of
  the atoms the structure already had are exactly where they were (counted by
  position, since MODELLER renames chains, renumbers residues and exchanges the
  names of equivalent atoms without moving them), and names any rebuilt
  residue that was not found in MODELLER's model and so was not refined.
• Membrane Builder: the build was stopped after one hour, a limit that was
  neither shown nor changeable, with "packmol-memgen timed out after 1 hour".
  A system of about 550,000 atoms needs longer than that. There is no limit
  now unless you set one, Ctrl-C stops the build cleanly, and stopping it
  (either way) also stops packmol, which packmol-memgen starts as a separate
  process.
• Membrane Builder, orientation with PPM3: choosing "Automatic (PPM3)" failed
  at once ("Protein orientation failed (PPM3 error)"), because packmol-memgen
  cannot take a protein file name with a directory in it and ProPrep passed
  ./protein_with_h.pdb. Past that, packmol-memgen packs the file PPM3
  writes, which holds only the residues PPM3 knows and no hydrogens: on 6R2Q,
  24,057 atoms became 10,769, without the 20 hemes, the residues ligating
  them, the protonation-state residues (HIE, HIP, LYN, GLH, CYX), the waters
  or the calcium ions. ProPrep now runs PPM3 itself, takes from it only where
  the membrane is (a rigid-body move, refused unless the atoms PPM3 kept fit
  within 0.01 Å), moves the complete structure and gives that to
  packmol-memgen as pre-oriented. PPM3 is the method behind the OPM database
  and is the one to try when MEMEMBED misplaces a protein: for 6R2Q, a
  beta-barrel complex that MEMEMBED leaves under the membrane in both of its
  modes, it reproduces OPM's orientation to within 1 Å.
• Redox Site Preparer: in a structure that also has a site needing new residue
  numbers (a c-type heme, which becomes three residues), only the second
  cysteine of each disulfide was renamed to CYX; the first stayed CYS. The
  structure looked finished and failed later: tLEaP stopped on "Could not find
  bond parameter for atom types: SH - S", in the Membrane Builder or the
  Topology Generator. The first cysteine had been renumbered for no reason
  (6R2Q: C:112 to 814) and its rename then looked for the old number, found
  nothing and said nothing. Sites that are edited in place (disulfides, the
  flavin, nicotinamide and pterin cofactors, "no transformation") are no
  longer renumbered, a step that is required and matches no atom is reported
  in red at any verbosity, and a cysteine already named CYX is left as it is.
  Structures prepared from a protein with both disulfides and c-type hemes
  should be checked for a CYS bonded to a CYX, and the Redox Site Preparer
  re-run.
• Membrane Builder: when tLEaP could not add the hydrogens, the builder gave no
  reason (it looked for one in tLEaP's stderr; tLEaP reports errors on stdout)
  and went on without asking, letting packmol-memgen protonate the protein.
  packmol-memgen then removes the residues it does not recognise and assigns
  protonation states of its own: on 6R2Q the bilayer was built around a
  protein with all 20 hemes removed and with one more ASH and one more GLH
  than the Protonation State Analyzer had assigned. The tLEaP errors are now
  listed, once each, with the path of leap.log, and continuing with
  packmol-memgen's own protonation is a question that says what it costs; the
  default is to stop. A bilayer built after the message "falling back to
  reduce" should be checked for its cofactors and rebuilt.
• Membrane Builder: packmol-memgen printed "Water model was not set. Using
  tip3p for ff14SB" under a review that had just named the water model. The
  model was never passed to it (--ffwat), so it picked one from the protein
  force field. Nothing built was affected: packmol-memgen uses the water model
  only in its own parametrization step, which ProPrep does not run, and the
  Topology Generator builds the system with the model you chose. The model is
  now passed and appears in the "Equivalent command". A water model taken from
  the force-field selection that packmol-memgen does not offer (FB4, OPC3-pol,
  ...) is left out, since passing it would stop packmol-memgen, and a line
  says why that changes nothing.
• undo: after a rewind, a module could go on reading and writing the
  workspace from before the rewind. The Redox Site Preparer, if it had been
  opened before the undo, transformed the structure correctly and wrote
  final_transformed_structure.pdb, but recorded it in the old workspace, so
  the Protonation State Analyzer (and anything else downstream) fell back to
  the filtered structure ("Using filtered structure"). An answer changed by
  the rewind could likewise be ignored by such a module. Modules are now
  rebuilt with the session. A session affected by this is put right by
  quitting and resuming it; results computed downstream of the rewind should
  be re-run.
• Redox Site Detector, template mode: a bond defined between two atoms of the
  same residue (pairs entered as 1-1, 2-2, ...; for example the heme
  C2A-CAA and the His/Cys CA-CB bonds that heme_bis_his_c_type asks
  for) was not reproduced on the other sites. The heme's own bonds were
  skipped ("no unused residue pair left") and each His/Cys CA-CB bond was
  drawn across to the other His/Cys of the site, 5 to 12 Å away; on 6R2Q this
  affected 19 of the 20 hemes. A bond captured within one residue is now
  applied within one residue, and a bond between two residues only between
  two. The site you configure by hand was always correct; sites filled in
  from its template should be re-run.
• Redox Site Detector: the viewer now shows the structure you selected for
  detection. Detection ran on the selected structure, but view opened the
  file the structure was first loaded from. With hydrogens removed at load
  and "H-Stripped" selected, the sites were found on the stripped structure
  and displayed on the deposited one, hydrogens included. The same held for
  any other selection (filtered, repaired, aligned, ...).

Installers

Self-contained installers (conda not required). Download, then bash ProPrep-1.22.0-<OS>.sh. Register for a free academic MODELLER key and put it in ~/.proprep/modeller_key, or run KEY_MODELLER=<key> bash ProPrep-1.22.0-<OS>.sh at install time.

SHA-256:

607e52d6fb0e67030a666ac79de456fdb34624bf6dfd87f57194544f47a4c520  ProPrep-1.22.0-Linux-x86_64.sh
d1c297b2329e08c0c62587f5e3733767fd582eb0b2400df49f97b8fbee0eacf7  ProPrep-1.22.0-MacOSX-arm64.sh
8ca8368953c1a7f93afc6542af7551fa5182be1d655622dc83d711d6833d9edd  ProPrep-1.22.0-MacOSX-x86_64.sh