PRODRG Frequently Asked Questions

This is an unordered list of some of the most frequently asked PRODRG questions with some answers. Please read ALL of this before posting "Help it doesn't work for me"-type questions to mailing lists. Do email me if you can't find the answer to your question here.

Q: I'm in a non-academic (i.e. commercial) environment. Can I use this server for free?

A: You are free to try a few test compounds (up to 5), then you should request a license.

Q: I would like to use PRODRG locally, where can I download a copy?

A: PRODRG executables are available under license, see here.

Q: I would like to run a database (> 50 compounds) of small molecules on your server. Is that OK?

A: Please email me first.

Q: I get a PDB file with all hydrogens but the topology files only contain information for hydrogens attached to non-carbon atoms?

A: That's right. PRODRG is intimately linked in with the concept of "united-atoms" which is used in many force fields to (drastically) reduce the total number of atoms. This is unlikely to change in the near future and indeed therefore makes PRODRG topologies unsuitable for use with NMR-type calculations or all-atom force fields.

Q: What is the most reliable way of input - drawings or coordinates?

A: Drawings by far. The main hurdle in defining the topology from coordinates is to correctly determine sp hybridisation. Coordinates usually only contain heavy atoms (think of a PDB file). Thus the only way to separate -C-O from -C=O is the C-O bond distance. Macromolecular crystallography isn't always very accurate, especially where ligands are concerned (there are quite a few papers on this). PRODRG operates on the principle "Garbage In - Garbage Out", although it will usually warn you if your coordinates contain strange geometry.

Q: How should I cite the use of PRODRG in my publications?

A: Please cite: A. W. Schüttelkopf and D. M. F. van Aalten (2004). PRODRG - a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D60, 1355–1363. A reprint can be obtained here.

Q: So I've got my GROMACS topology - now what?

A: John Kerrigan (http://www2.umdnj.edu/~kerrigje) has made an excellent tutorial on how to use PRODRG topologies for enzyme-ligand systems in the GROMACS MD program. Get a copy here.

Q: Do you have a measure of the reliability of PRODRG?

A: I have recently performed several tests which will hopefully be published somewhere in the not-too-distant future. In the mean time – below you can see distributions of deviations on bonds, angles and planes of about 40000 entries from the Cambridge small molecule database minimized with GROMOS87 and then compared to the (crystallographic) starting structure. Apart from some flukes (you don't even want to know what kinds of complete fantasy molecules these are) this looks reasonable (I think).

Q: The atomic charges don't always come out right!

A: This is a well known limitation. PRODRG works with the concept of charge groups, which are defined as a group of bonded atoms with an integer charge. E.g. -COO would have the C (with a slight positive charge) and the two O's (with an equal negative charge) in one "charge group" with the total charge being -1. Thus in order for PRODRG to assign atomic charges it needs to be able to recognise the charge groups first. This is particularly difficult in ring systems with nitrogens, and several charge group definitions (e.g. C-Cl) or still missing. I would definitely recommend that you check these charges before starting your 2 microsecond simulation.

Q: PRODRG doesn't work for me. Do you know another program?

A: Gerard Kleywegt in Uppsala has an excellent database (HIC-Up) of small molecule data (including CNS topologies) based on the PDB. You can find it here. Also there is a lot of useful info at the EBI MSD site.

Q: PRODRG doesn't protonate my molecule the way I want it.

A: You can change the default hydrogen placement by adding the commands

ADDHYD atomname

DELHYD atomname

to your input file/drawing. Note that the names you give must be the atom names as output by PRODRG, not the input names (if there is a difference).

Q: PRODRG doesn't correctly determine the hybridization of an atom in my molecule.

A: This can be fixed by adding the command

PATCH atomname n

to your input file/drawing, where n is 1 to force sp hybridization, 2 to force sp2 hybridization and 3 to force sp3 hybridization.

Q: Why does PRODRG insist on renaming my atoms? This is a major pain!

A: Most refinement programs require unique atom identifiers (names). PRODRG therefore checks for duplicate atoms names in your input, and if it finds them all atoms are renamed. You can prevent this by using a simple trick. Consider the following input PDB file, corresponding to a disaccharide:

ATOM   6061  C1  NAG J 100      35.115  45.254  26.962  1.00 80.61      J   
ATOM   6062  O1  NAG J 100      35.377  46.459  26.322  1.00 82.53      J   
ATOM   6063  C2  NAG J 100      33.914  45.427  27.904  1.00 79.68      J   
ATOM   6064  N2  NAG J 100      34.342  46.212  29.048  1.00 76.74      J   
ATOM   6065  C7  NAG J 100      33.703  47.331  29.391  1.00 77.06      J   
ATOM   6066  O7  NAG J 100      32.759  47.811  28.741  1.00 73.53      J   
ATOM   6067  C8  NAG J 100      34.194  48.023  30.661  1.00 75.36      J   
ATOM   6068  C3  NAG J 100      33.328  44.080  28.404  1.00 79.56      J   
ATOM   6069  O3  NAG J 100      32.006  44.297  28.880  1.00 76.89      J   
ATOM   6070  C4  NAG J 100      33.288  42.978  27.322  1.00 80.90      J   
ATOM   6071  O4  NAG J 100      33.117  41.684  27.949  1.00 81.05      J   
ATOM   6072  C5  NAG J 100      34.596  42.967  26.526  1.00 82.74      J   
ATOM   6073  O5  NAG J 100      34.836  44.274  25.957  1.00 81.58      J   
ATOM   6074  C6  NAG J 100      34.610  41.950  25.387  1.00 83.21      J   
ATOM   6075  O6  NAG J 100      33.690  42.295  24.361  1.00 84.17      J   
ATOM   6076  C1  NAG J 101      31.840  41.135  27.969  1.00 80.03      J   
ATOM   6077  C2  NAG J 101      31.931  39.609  28.068  1.00 79.65      J   
ATOM   6078  N2  NAG J 101      32.632  39.057  26.928  1.00 81.28      J   
ATOM   6079  C7  NAG J 101      33.475  38.050  27.115  1.00 83.77      J   
ATOM   6080  O7  NAG J 101      33.097  36.900  27.372  1.00 87.31      J   
ATOM   6081  C8  NAG J 101      34.959  38.362  27.030  1.00 83.69      J   
ATOM   6082  C3  NAG J 101      30.521  39.020  28.164  1.00 78.11      J   
ATOM   6083  O3  NAG J 101      30.580  37.601  28.249  1.00 77.92      J   
ATOM   6084  C4  NAG J 101      29.787  39.600  29.388  1.00 76.01      J   
ATOM   6085  O4  NAG J 101      28.418  39.108  29.368  1.00 73.39      J   
ATOM   6086  C5  NAG J 101      29.818  41.151  29.285  1.00 76.56      J   
ATOM   6087  O5  NAG J 101      31.170  41.646  29.129  1.00 78.56      J   
ATOM   6088  C6  NAG J 101      29.264  41.874  30.482  1.00 74.25      J   
ATOM   6089  O6  NAG J 101      28.869  43.191  30.121  1.00 70.64      J

Each atom name occurs twice, so the output will contain atom names xAA to xBC. To prevent this, include an additional character at the end of your atom name:

ATOM   6061  C1A NAG J 100      35.115  45.254  26.962  1.00 80.61      J   
ATOM   6062  O1A NAG J 100      35.377  46.459  26.322  1.00 82.53      J   
ATOM   6063  C2A NAG J 100      33.914  45.427  27.904  1.00 79.68      J   
ATOM   6064  N2A NAG J 100      34.342  46.212  29.048  1.00 76.74      J   
ATOM   6065  C7A NAG J 100      33.703  47.331  29.391  1.00 77.06      J   
ATOM   6066  O7A NAG J 100      32.759  47.811  28.741  1.00 73.53      J   
ATOM   6067  C8A NAG J 100      34.194  48.023  30.661  1.00 75.36      J   
ATOM   6068  C3A NAG J 100      33.328  44.080  28.404  1.00 79.56      J   
ATOM   6069  O3A NAG J 100      32.006  44.297  28.880  1.00 76.89      J   
ATOM   6070  C4A NAG J 100      33.288  42.978  27.322  1.00 80.90      J   
ATOM   6071  O4A NAG J 100      33.117  41.684  27.949  1.00 81.05      J   
ATOM   6072  C5A NAG J 100      34.596  42.967  26.526  1.00 82.74      J   
ATOM   6073  O5A NAG J 100      34.836  44.274  25.957  1.00 81.58      J   
ATOM   6074  C6A NAG J 100      34.610  41.950  25.387  1.00 83.21      J   
ATOM   6075  O6A NAG J 100      33.690  42.295  24.361  1.00 84.17      J   
ATOM   6076  C1B NAG J 101      31.840  41.135  27.969  1.00 80.03      J   
ATOM   6077  C2B NAG J 101      31.931  39.609  28.068  1.00 79.65      J   
ATOM   6078  N2B NAG J 101      32.632  39.057  26.928  1.00 81.28      J   
ATOM   6079  C7B NAG J 101      33.475  38.050  27.115  1.00 83.77      J   
ATOM   6080  O7B NAG J 101      33.097  36.900  27.372  1.00 87.31      J   
ATOM   6081  C8B NAG J 101      34.959  38.362  27.030  1.00 83.69      J   
ATOM   6082  C3B NAG J 101      30.521  39.020  28.164  1.00 78.11      J   
ATOM   6083  O3B NAG J 101      30.580  37.601  28.249  1.00 77.92      J   
ATOM   6084  C4B NAG J 101      29.787  39.600  29.388  1.00 76.01      J   
ATOM   6085  O4B NAG J 101      28.418  39.108  29.368  1.00 73.39      J   
ATOM   6086  C5B NAG J 101      29.818  41.151  29.285  1.00 76.56      J   
ATOM   6087  O5B NAG J 101      31.170  41.646  29.129  1.00 78.56      J   
ATOM   6088  C6B NAG J 101      29.264  41.874  30.482  1.00 74.25      J   
ATOM   6089  O6B NAG J 101      28.869  43.191  30.121  1.00 70.64      J

Q: Are there problems with using more than one PRODRG topolgy in CNS?

A: Yes and no. First of all, make sure the molecule name is different in the different topology and parameter files – using the name DRG for two different molecules will cause trouble. In addition you will get problems because PRODRG defines its own atom types in CNS – but the names it uses to describe the types are assigned using a fixed pattern (e.g. C_AA, C_AB, N_AC etc.) and this results in the same name referring two different chemistries in two different molecules. Consider the situation of having a refinement with protein, a glycerol and an AMP molecule, the latter two with PRODRG topologies. If you read in your glycerol parameter/topology files which define an atom (e.g.) C_AA and after that you read in your AMP parameter file which (RE!!!)-defines C_AA that means the AMP atom definition will be used for your glycerol - with disastrous consequences. Thus do a search and replace _ with something else (e.g. x) for the AMP parameter/topology files.