WHAT IF Check report

This file was created 2011-12-16 from WHAT_CHECK output by a conversion script. If you are new to WHAT_CHECK, please study the pdbreport pages. There also exists a legend to the output.

Please note that you are looking at an abridged version of the output (all checks that gave normal results have been removed from this report). You can have a look at the Full report instead.

Verification log for pdb1jdj.ent

Checks that need to be done early-on in validation

Warning: Ligands for which a topology was generated automatically

The topology for the ligands in the table below were determined automatically. WHAT IF uses a local copy of Daan van Aalten's Dundee PRODRG server to automatically generate topology information for ligands. For this PDB file that seems to have gone fine, but be aware that automatic topology generation is a complicated task. So, if you get messages that you fail to understand or that you believe are wrong, and one of these ligands is involved, then check the ligand topology first.

 347 MYS   ( 500-)  A  -
 348 CFP   ( 367-)  A  -

Non-validating, descriptive output paragraph

Note: Ramachandran plot

In this Ramachandran plot x-signs represent glycines, squares represent prolines, and plus-signs represent the other residues. If too many plus- signs fall outside the contoured areas then the molecule is poorly refined (or worse). Proline can only occur in the narrow region around phi=-60 that also falls within the other contour islands.

In a colour picture, the residues that are part of a helix are shown in blue, strand residues in red. Preferred regions for helical residues are drawn in blue, for strand residues in red, and for all other residues in green. A full explanation of the Ramachandran plot together with a series of examples can be found at the WHAT_CHECK website.

Chain identifier: A

Coordinate problems, unexpected atoms, B-factor and occupancy checks

Warning: Occupancies atoms do not add up to 1.0.

In principle, the occupancy of all alternates of one atom should add up till 1.0. A valid exception is the missing atom (i.e. an atom not seen in the electron density) that is allowed to have a 0.0 occupancy. Sometimes this even happens when there are no alternate atoms given...

Atoms want to move. That is the direct result of the second law of thermodynamics, in a somewhat weird way of thinking. Any way, many atoms seem to have more than one position where they like to sit, and they jump between them. The population difference between those sites (which is related to their energy differences) is seen in the occupancy factors. As also for atoms it is 'to be or not to be', these occupancies should add up to 1.0. Obviously, it is possible that they add up to a number less than 1.0, in cases where there are yet more, but undetected' rotamers/positions in play, but also in those cases a warning is in place as the information shown in the PDB file is less certain than it could have been. The residues listed below contain atoms that have an occupancy greater than zero, but all their alternates do not add up to one.

WARNING. Presently WHAT CHECK only deals with a maximum of two alternate positions. A small number of atoms in the PDB has three alternates. In those cases the warning given here should obviously be neglected! In a next release we will try to fix this.

 227 MET   ( 235-)  A    0.50

Warning: What type of B-factor?

WHAT IF does not yet know well how to cope with B-factors in case TLS has been used. It simply assumes that the B-factor listed on the ATOM and HETATM cards are the total B-factors. When TLS refinement is used that assumption sometimes is not correct. TLS seems not mentioned in the header of the PDB file. But anyway, if WHAT IF complains about your B-factors, and you think that they are OK, then check for TLS related B-factor problems first.

Obviously, the temperature at which the X-ray data was collected has some importance too:

Crystal temperature (K) :125.000

Error: The B-factors of bonded atoms show signs of over-refinement

For each of the bond types in a protein a distribution was derived for the difference between the square roots of the B-factors of the two atoms. All bonds in the current protein were scored against these distributions. The number given below is the RMS Z-score over the structure. For a structure with completely restrained B-factors within residues, this value will be around 0.35, for extremely high resolution structures refined with free isotropic B-factors this number is expected to be near 1.0. Any value over 1.5 is sign of severe over-refinement of B-factors.

RMS Z-score : 1.514 over 2298 bonds
Average difference in B over a bond : 4.28
RMS difference in B over a bond : 6.05

Note: B-factor plot

The average atomic B-factor per residue is plotted as function of the residue number.

Chain identifier: A

Nomenclature related problems

Warning: Phenylalanine convention problem

The phenylalanine residues listed in the table below have their chi-2 not between -90.0 and 90.0.

  13 PHE   (  21-)  A
  18 PHE   (  26-)  A
  55 PHE   (  63-)  A
  83 PHE   (  91-)  A
  89 PHE   (  97-)  A
  94 PHE   ( 102-)  A
 148 PHE   ( 156-)  A
 248 PHE   ( 256-)  A

Warning: Aspartic acid convention problem

The aspartic acid residues listed in the table below have their chi-2 not between -90.0 and 90.0, or their proton on OD1 instead of OD2.

 166 ASP   ( 174-)  A
 181 ASP   ( 189-)  A
 191 ASP   ( 199-)  A
 243 ASP   ( 251-)  A
 255 ASP   ( 263-)  A
 326 ASP   ( 337-)  A
 330 ASP   ( 341-)  A

Warning: Glutamic acid convention problem

The glutamic acid residues listed in the table below have their chi-3 outside the -90.0 to 90.0 range, or their proton on OE1 instead of OE2.

  40 GLU   (  48-)  A
  51 GLU   (  59-)  A

Geometric checks

Error: Nomenclature error(s)

Checking for a hand-check. WHAT IF has over the course of this session already corrected the handedness of atoms in several residues. These were administrative corrections. These residues are listed here.

  40 GLU   (  48-)  A
  51 GLU   (  59-)  A
 166 ASP   ( 174-)  A
 181 ASP   ( 189-)  A
 191 ASP   ( 199-)  A
 243 ASP   ( 251-)  A
 255 ASP   ( 263-)  A
 326 ASP   ( 337-)  A
 330 ASP   ( 341-)  A

Torsion-related checks

Warning: Torsion angle evaluation shows unusual residues

The residues listed in the table below contain bad or abnormal torsion angles.

These scores give an impression of how `normal' the torsion angles in protein residues are. All torsion angles except omega are used for calculating a `normality' score. Average values and standard deviations were obtained from the residues in the WHAT IF database. These are used to calculate Z-scores. A residue with a Z-score of below -2.0 is poor, and a score of less than -3.0 is worrying. For such residues more than one torsion angle is in a highly unlikely position.

 309 PRO   ( 320-)  A    -2.7
  56 LEU   (  64-)  A    -2.5
  68 THR   (  76-)  A    -2.4
 167 ILE   ( 175-)  A    -2.3
 127 PRO   ( 135-)  A    -2.2
  99 GLY   ( 107-)  A    -2.2
 189 THR   ( 197-)  A    -2.1
  14 GLY   (  22-)  A    -2.1
  50 ARG   (  58-)  A    -2.1

Warning: Backbone evaluation reveals unusual conformations

The residues listed in the table below have abnormal backbone torsion angles.

Residues with `forbidden' phi-psi combinations are listed, as well as residues with unusual omega angles (deviating by more than 3 sigma from the normal value). Please note that it is normal if about 5 percent of the residues is listed here as having unusual phi-psi combinations.

  99 GLY   ( 107-)  A  Poor phi/psi
 124 LEU   ( 132-)  A  Poor phi/psi
 182 ARG   ( 190-)  A  Poor phi/psi
 191 ASP   ( 199-)  A  Poor phi/psi
 305 LYS   ( 316-)  A  Poor phi/psi
 chi-1/chi-2 correlation Z-score : -0.457

Warning: Unusual backbone conformations

For the residues listed in the table below, the backbone formed by itself and two neighbouring residues on either side is in a conformation that is not seen very often in the database of solved protein structures. The number given in the table is the number of similar backbone conformations in the database with the same amino acid in the centre.

For this check, backbone conformations are compared with database structures using C-alpha superpositions with some restraints on the backbone oxygen positions.

A residue mentioned in the table can be part of a strange loop, or there might be something wrong with it or its directly surrounding residues. There are a few of these in every protein, but in any case it is worth looking at!

  13 PHE   (  21-)  A      0
  29 LYS   (  37-)  A      0
  30 CYS   (  38-)  A      0
  31 ARG   (  39-)  A      0
  38 MET   (  46-)  A      0
  50 ARG   (  58-)  A      0
  54 LEU   (  62-)  A      0
  55 PHE   (  63-)  A      0
  57 LYS   (  65-)  A      0
  76 ASN   (  84-)  A      0
  79 GLU   (  87-)  A      0
  83 PHE   (  91-)  A      0
  84 VAL   (  92-)  A      0
  96 LYS   ( 104-)  A      0
  97 SER   ( 105-)  A      0
 115 CYS   ( 123-)  A      0
 117 LYS   ( 125-)  A      0
 121 ARG   ( 129-)  A      0
 124 LEU   ( 132-)  A      0
 134 PHE   ( 142-)  A      0
 144 ALA   ( 152-)  A      0
 146 PRO   ( 154-)  A      0
 147 SER   ( 155-)  A      0
 154 THR   ( 162-)  A      0
 157 PHE   ( 165-)  A      0
And so on for a total of 98 lines.

Warning: Omega angles too tightly restrained

The omega angles for trans-peptide bonds in a structure are expected to give a gaussian distribution with the average around +178 degrees and a standard deviation around 5.5 degrees. These expected values were obtained from very accurately determined structures. Many protein structures are too tightly restrained. This seems to be the case with the current structure too, as the observed standard deviation is below 4.0 degrees.

Standard deviation of omega values : 1.101

Warning: Backbone oxygen evaluation

The residues listed in the table below have an unusual backbone oxygen position.

For each of the residues in the structure, a search was performed to find 5-residue stretches in the WHAT IF database with superposable C-alpha coordinates, and some restraining on the neighbouring backbone oxygens.

In the following table the RMS distance between the backbone oxygen positions of these matching structures in the database and the position of the backbone oxygen atom in the current residue is given. If this number is larger than 1.5 a significant number of structures in the database show an alternative position for the backbone oxygen. If the number is larger than 2.0 most matching backbone fragments in the database have the peptide plane flipped. A manual check needs to be performed to assess whether the experimental data can support that alternative as well. The number in the last column is the number of database hits (maximum 80) used in the calculation. It is "normal" that some glycine residues show up in this list, but they are still worth checking!

 127 PRO   ( 135-)  A   1.84   11

Warning: Unusual PRO puckering phases

The proline residues listed in the table below have a puckering phase that is not expected to occur in protein structures. Puckering parameters were calculated by the method of Cremer and Pople [REF]. Normal PRO rings approximately show a so-called envelope conformation with the C-gamma atom above the plane of the ring (phi=+72 degrees), or a half-chair conformation with C-gamma below and C-beta above the plane of the ring (phi=-90 degrees). If phi deviates strongly from these values, this is indicative of a very strange conformation for a PRO residue, and definitely requires a manual check of the data. Be aware that this is a warning with a low confidence level. See: Who checks the checkers? Four validation tools applied to eight atomic resolution structures [REF].

 146 PRO   ( 154-)  A    51.4 half-chair C-delta/C-gamma (54 degrees)

Bump checks

Error: Abnormally short interatomic distances

The pairs of atoms listed in the table below have an unusually short interactomic distance; each bump is listed in only one direction.

The contact distances of all atom pairs have been checked. Two atoms are said to `bump' if they are closer than the sum of their Van der Waals radii minus 0.40 Angstrom. For hydrogen bonded pairs a tolerance of 0.55 Angstrom is used. The first number in the table tells you how much shorter that specific contact is than the acceptable limit. The second distance is the distance between the centres of the two atoms. Although we believe that two water atoms at 2.4 A distance are too close, we only report water pairs that are closer than this rather short distance.

The last text-item on each line represents the status of the atom pair. If the final column contains the text 'HB', the bump criterion was relaxed because there could be a hydrogen bond. Similarly relaxed criteria are used for 1-3 and 1-4 interactions (listed as 'B2' and 'B3', respectively). BL indicates that the B-factors of the clashing atoms have a low B-factor thereby making this clash even more worrisome. INTRA and INTER indicate whether the clashes are between atoms in the same asymmetric unit, or atoms in symmetry related asymmetric units, respectively.

 266 ARG   ( 274-)  A      NH1 <->  286 ALA   ( 297-)  A      CB     0.23    2.87  INTRA BF
 285 ARG   ( 293-)  A      C   <->  286 ALA   ( 297-)  A      N      0.23    2.67  INTRA BF
 322 LYS   ( 333-)  A      NZ  <->  330 ASP   ( 341-)  A      OD2    0.20    2.50  INTRA
   8 ASN   (  16-)  A      N   <->   79 GLU   (  87-)  A      OE1    0.16    2.54  INTRA
  15 SER   (  23-)  A      OG  <->   37 HIS   (  45-)  A      ND1    0.16    2.54  INTRA
 137 SER   ( 145-)  A      N   <->  138 PRO   ( 146-)  A      CD     0.16    2.84  INTRA BF
   5 LEU   (  13-)  A      CD2 <->  175 ARG   ( 183-)  A      NH2    0.14    2.96  INTRA BF
 172 ARG   ( 180-)  A      NE  <->  349 HOH   ( 617 )  A      O      0.13    2.57  INTRA BF
 243 ASP   ( 251-)  A      OD1 <->  245 SER   ( 253-)  A      N      0.11    2.59  INTRA BL
 137 SER   ( 145-)  A      O   <->  140 LEU   ( 148-)  A      N      0.09    2.61  INTRA BF
   9 LYS   (  17-)  A      NZ  <->   76 ASN   (  84-)  A      O      0.08    2.62  INTRA
 303 GLN   ( 314-)  A      NE2 <->  349 HOH   ( 626 )  A      O      0.08    2.62  INTRA BF
 232 GLU   ( 240-)  A      OE2 <->  310 LEU   ( 321-)  A      N      0.06    2.64  INTRA BL
  47 ASN   (  55-)  A      O   <->   50 ARG   (  58-)  A      CD     0.06    2.74  INTRA BF
 128 ALA   ( 136-)  A      N   <->  196 GLU   ( 204-)  A      OE2    0.04    2.66  INTRA BL
  98 GLY   ( 106-)  A      O   <->  102 ILE   ( 110-)  A      N      0.04    2.66  INTRA BL
   3 GLU   (  11-)  A      O   <->  175 ARG   ( 183-)  A      NH1    0.04    2.66  INTRA BF
  51 GLU   (  59-)  A      OE2 <->   58 GLY   (  66-)  A      N      0.04    2.66  INTRA BF
  84 VAL   (  92-)  A      N   <->   85 ILE   (  93-)  A      N      0.03    2.57  INTRA BL
 150 ILE   ( 158-)  A      CG2 <->  151 GLU   ( 159-)  A      N      0.03    2.97  INTRA
  81 ILE   (  89-)  A      O   <->  113 LEU   ( 121-)  A      N      0.02    2.68  INTRA BL
 121 ARG   ( 129-)  A      NE  <->  349 HOH   ( 652 )  A      O      0.02    2.68  INTRA BF
 120 GLU   ( 128-)  A      O   <->  124 LEU   ( 132-)  A      N      0.02    2.68  INTRA BL
 149 ALA   ( 157-)  A      O   <->  153 ALA   ( 161-)  A      N      0.01    2.69  INTRA BL
 137 SER   ( 145-)  A      C   <->  139 LEU   ( 147-)  A      N      0.01    2.89  INTRA BF

Packing, accessibility and threading

Note: Inside/Outside RMS Z-score plot

The Inside/Outside distribution normality RMS Z-score over a 15 residue window is plotted as function of the residue number. High areas in the plot (above 1.5) indicate unusual inside/outside patterns.

Chain identifier: A

Warning: Abnormal packing environment for some residues

The residues listed in the table below have an unusual packing environment.

The packing environment of the residues is compared with the average packing environment for all residues of the same type in good PDB files. A low packing score can indicate one of several things: Poor packing, misthreading of the sequence through the density, crystal contacts, contacts with a co-factor, or the residue is part of the active site. It is not uncommon to see a few of these, but in any case this requires further inspection of the residue.

 336 LEU   ( 347-)  A      -7.00
 345 PHE   ( 356-)  A      -6.69
 307 LYS   ( 318-)  A      -6.29
 117 LYS   ( 125-)  A      -5.94
 341 LEU   ( 352-)  A      -5.78
 344 LEU   ( 355-)  A      -5.40
  38 MET   (  46-)  A      -5.04

Warning: Abnormal packing environment for sequential residues

A stretch of at least three sequential residues with a questionable packing environment was found. This could indicate that these residues are part of a strange loop. It might also be an indication of misthreading in the density. However, it can also indicate that one or more residues in this stretch have other problems such as, for example, missing atoms, very weird angles or bond lengths, etc.

The table below lists the first and last residue in each stretch found, as well as the average residue score of the series.

  95 GLU   ( 103-)  A        97 - SER    105- ( A)         -4.17
 336 LEU   ( 347-)  A       339 - GLU    350- ( A)         -5.16

Note: Quality value plot

The quality value smoothed over a 10 residue window is plotted as function of the residue number. Low areas in the plot (below -2.0) indicate unusual packing.

Chain identifier: A

Note: Second generation quality Z-score plot

The second generation quality Z-score smoothed over a 10 residue window is plotted as function of the residue number. Low areas in the plot (below -1.3) indicate unusual packing.

Chain identifier: A

Water, ion, and hydrogenbond related checks

Error: Water molecules without hydrogen bonds

The water molecules listed in the table below do not form any hydrogen bonds, neither with the protein or DNA/RNA, nor with other water molecules. This is a strong indication of a refinement problem. The last number on each line is the identifier of the water molecule in the input file.

 349 HOH   ( 643 )  A      O
Marked this atom as acceptor  348 CFP  ( 367-) A     CL6
Marked this atom as acceptor  348 CFP  ( 367-) A      F2

Warning: Buried unsatisfied hydrogen bond donors

The buried hydrogen bond donors listed in the table below have a hydrogen atom that is not involved in a hydrogen bond in the optimized hydrogen bond network.

Hydrogen bond donors that are buried inside the protein normally use all of their hydrogens to form hydrogen bonds within the protein. If there are any non hydrogen bonded buried hydrogen bond donors in the structure they will be listed here. In very good structures the number of listed atoms will tend to zero.

Waters are not listed by this option.

  39 ASN   (  47-)  A      N
  80 ILE   (  88-)  A      N
  87 THR   (  95-)  A      OG1
 175 ARG   ( 183-)  A      NH1
 244 GLY   ( 252-)  A      N
 257 GLN   ( 265-)  A      NE2
 281 GLU   ( 289-)  A      N
 295 ASP   ( 306-)  A      N

Warning: Unusual water packing

We implemented the ion valence determination method of Brown and Wu [REF] similar to Nayal and Di Cera [REF] and Mueller, Koepke and Sheldrick [REF]. It must be stated that the validation of ions in PDB files is very difficult. Ideal ion-ligand distances often differ no more than 0.1 Angstrom, and in a 2.0 Angstrom resolution structure 0.1 Angstrom is not very much. Nayal and Di Cera showed that this method nevertheless has great potential for detecting water molecules that actually should be metal ions. The method has not been extensively validated, though. Part of our implementation (comparing waters with multiple ion types) is even fully new and despite that we see it work well in the few cases that are trivial, we must emphasize that this method is untested.

The score listed is the valency score. This number should be close to (preferably a bit above) 1.0 for the suggested ion to be a likely alternative for the water molecule. Ions listed in brackets are good alternate choices. *1 indicates that the suggested ion-type has been observed elsewhere in the PDB file too. *2 indicates that the suggested ion-type has been observed in the REMARK 280 cards of the PDB file. Ion-B and ION-B indicate that the B-factor of this water is high, or very high, respectively. H2O-B indicates that the B-factors of atoms that surround this water/ion are suspicious. See: swift.cmbi.ru.nl/teach/theory/ for a detailed explanation.

 349 HOH   ( 513 )  A      O  1.07  K  4

Final summary

Note: Summary report for users of a structure

This is an overall summary of the quality of the structure as compared with current reliable structures. This summary is most useful for biologists seeking a good structure to use for modelling calculations.

The second part of the table mostly gives an impression of how well the model conforms to common refinement restraint values. The first part of the table shows a number of global quality indicators.

Structure Z-scores, positive is better than average:

  1st generation packing quality :   0.369
  2nd generation packing quality :  -0.969
  Ramachandran plot appearance   :  -0.252
  chi-1/chi-2 rotamer normality  :  -0.457
  Backbone conformation          :   0.749

RMS Z-scores, should be close to 1.0:
  Bond lengths                   :   0.244 (tight)
  Bond angles                    :   0.509 (tight)
  Omega angle restraints         :   0.200 (tight)
  Side chain planarity           :   0.197 (tight)
  Improper dihedral distribution :   0.527
  B-factor distribution          :   1.514 (loose)
  Inside/Outside distribution    :   1.006

Note: Summary report for depositors of a structure

This is an overall summary of the quality of the X-ray structure as compared with structures solved at similar resolutions. This summary can be useful for a crystallographer to see if the structure makes the best possible use of the data. Warning. This table works well for structures solved in the resolution range of the structures in the WHAT IF database, which is presently (summer 2008) mainly 1.1 - 1.3 Angstrom. The further the resolution of your file deviates from this range the more meaningless this table becomes.

The second part of the table mostly gives an impression of how well the model conforms to common refinement restraint values. The first part of the table shows a number of global quality indicators, which have been calibrated against structures of similar resolution.

Resolution found in PDB file : 2.20

Structure Z-scores, positive is better than average:

  1st generation packing quality :   0.9
  2nd generation packing quality :  -0.4
  Ramachandran plot appearance   :   0.9
  chi-1/chi-2 rotamer normality  :   0.7
  Backbone conformation          :   0.7

RMS Z-scores, should be close to 1.0:
  Bond lengths                   :   0.244 (tight)
  Bond angles                    :   0.509 (tight)
  Omega angle restraints         :   0.200 (tight)
  Side chain planarity           :   0.197 (tight)
  Improper dihedral distribution :   0.527
  B-factor distribution          :   1.514 (loose)
  Inside/Outside distribution    :   1.006

      WHAT IF: a molecular modelling and drug design program,
    J. Mol. Graph. 8, 52--56 (1990).

WHAT_CHECK (verification routines from WHAT IF)
    R.W.W.Hooft, G.Vriend, C.Sander and E.E.Abola,
      Errors in protein structures
    Nature 381, 272 (1996).
    (see also http://swift.cmbi.ru.nl/gv/whatcheck for a course and extra inform

Bond lengths and angles, protein residues
    R.Engh and R.Huber,
      Accurate bond and angle parameters for X-ray protein structure
    Acta Crystallogr. A47, 392--400 (1991).

Bond lengths and angles, DNA/RNA
    G.Parkinson, J.Voitechovsky, L.Clowney, A.T.Bruenger and H.Berman,
      New parameters for the refinement of nucleic acid-containing structures
    Acta Crystallogr. D52, 57--64 (1996).

    W.Kabsch and C.Sander,
      Dictionary of protein secondary structure: pattern
      recognition of hydrogen bond and geometrical features
    Biopolymers 22, 2577--2637 (1983).

Hydrogen bond networks
    R.W.W.Hooft, C.Sander and G.Vriend,
      Positioning hydrogen atoms by optimizing hydrogen bond networks in
      protein structures
    PROTEINS, 26, 363--376 (1996).

Matthews' Coefficient
      Solvent content of Protein Crystals
    J. Mol. Biol. 33, 491--497 (1968).

Protein side chain planarity
    R.W.W. Hooft, C. Sander and G. Vriend,
      Verification of protein structures: side-chain planarity
    J. Appl. Cryst. 29, 714--716 (1996).

Puckering parameters
    D.Cremer and J.A.Pople,
      A general definition of ring puckering coordinates
    J. Am. Chem. Soc. 97, 1354--1358 (1975).

Quality Control
    G.Vriend and C.Sander,
      Quality control of protein models: directional atomic
      contact analysis,
    J. Appl. Cryst. 26, 47--60 (1993).

Ramachandran plot
    G.N.Ramachandran, C.Ramakrishnan and V.Sasisekharan,
      Stereochemistry of Polypeptide Chain Conformations
    J. Mol. Biol. 7, 95--99 (1963).

Symmetry Checks
    R.W.W.Hooft, C.Sander and G.Vriend,
      Reconstruction of symmetry related molecules from protein
      data bank (PDB) files
    J. Appl. Cryst. 27, 1006--1009 (1994).

Ion Checks
    I.D.Brown and K.K.Wu,
      Empirical Parameters for Calculating Cation-Oxygen Bond Valences
    Acta Cryst. B32, 1957--1959 (1975).

    M.Nayal and E.Di Cera,
      Valence Screening of Water in Protein Crystals Reveals Potential Na+
      Binding Sites
    J.Mol.Biol. 256 228--234 (1996).

    P.Mueller, S.Koepke and G.M.Sheldrick,
      Is the bond-valence method able to identify metal atoms in protein
    Acta Cryst. D 59 32--37 (2003).

Checking checks
    K.Wilson, C.Sander, R.W.W.Hooft, G.Vriend, et al.
      Who checks the checkers
    J.Mol.Biol. (1998) 276,417-436.