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Documentation

  1. Information Content
  2. Sources of Affinity Data
  3. Description of Data Fields
  4. Searching and Browsing the Database
  5. Adding New Data
  6. Acknowledgement and Disclaimer

  1. Information Content
  2. The Affinity Database 'AffinDB' contains affinity data for protein-ligand complexes of the PDB. Its purpose is to provide direct and free access to the experimental affinity of a given complex structure.
    As of Wednesday, September 20th, 2017, AffinDB contains 748 affinity values covering 474 different PDB complexes. More than one affinity value may be associated with a single PDB complex, which is most frequently due to multiple references reporting affinity data for the same complex.

  3. Sources of Affinity Data
  4. Affinity data are exclusively obtained from the scientific literature. Both 'primary' and 'secondary' references are taken into account:
    • A primary reference is a paper describing the original work of affinity measurement for the corresponding protein-ligand complex.
    • A secondary reference is any other paper that reports an affinity value for a PDB complex; common examples are publications which include compilations of affinity data for a specific purpose.

  5. Description of Data Fields
  6. AffinDB provides access to data in three different forms:
    I. Summary information for PDB entry
    II. Affinity information window
    III. Tabular reports

    I. Summary information for PDB entry
    PDB information. For every experimental structure in the PDB, some basic information is provided, regardless of the presence or absence of a small-molecule ligand and regardless whether affinity data are already available or not. This includes the name of the protein or protein class (as given in the header information of the PDB file), the E.C. number in case of an enzyme (if available), the source of the protein, the resolution of the crystal structure, and the name of the authors of the PDB structure. In addition, each PDB code is linked to the following external databases: PDB, Relibase, MSD, SCOP, PDBsum.

    Ligand information. If the PDB structure corresponds to a complex with a small-molecule ligand consisting of more than five non-hydrogen atoms, the following information about the ligand is displayed: the entry code, the chemical name, the molecular weight (in Dalton), and a 2D drawing of the ligand structure (generated with MarvinView). This ligand information is provided regardless whether affinity data are already available or not.

    Affinity information. If an affinity value for the ligand is available in the database, it is displayed below the ligand structure, along with the first author and the year of the publication which reports this value. If additional affinity values are available from other references, these are displayed as well, each in a separate line. Further details can be requested for each affinity entry by following the 'Details' link or by checking the boxes at the beginning of each affinity information line and clicking on the 'Show details for selection' button. All details are displayed in a separate affinity information window.

    II. Affinity information window
    If available, the following data are provided for each affinity entry:
    • Affinity
      The affinity value is normally shown in the same form as published in the specified reference, i.e., without any conversion of type or unit. If available, experimental uncertainties or error margins are shown as well.
      The affinity may be given in one of the following types ('measurands'):
      • Ki: enzyme inhibition constant;
      • IC50: inhibitor concentration at 50% inhibition of an enzyme;
      • Kd: dissociation constant;
      • Ka: association constant;
      • ΔG: Gibbs free energy of binding (for association reaction).
      In addition, the values may be given as negative base-10 logarithms, i.e., as pKi, pKd, pIC50 (relative to the standard concentration of 1 mol/l).
    • Experimental conditions
      In this section, the experimental method and conditions of the affinity measurement are reported, if specified in the corresponding reference:
      • Method: a keyword or brief statement to characterize the method by which the affinity value was determined.
      • Temperature: the temperature at which the measurement was carried out.
      • pH: the pH value at which the measurement was carried out.
      • Buffer: the type of buffer (normally specified by the abbreviation used in the corresponding reference).
      • Reagents/Additives: any other significant reagents or additives present in the solution upon measurement, if reported in the reference.
    • Literature
      The reference from which the affinity value was taken is specified as follows:
      • Author: only the first author is given.
      • Journal/Source: title of the journal, volume, year, and first page of the publication.
      • Literature primary: if 'yes', the reference is an original work reporting the affinity measurement for the corresponding protein-ligand complex; if 'no', this is not the case, which means that the affinity value for the PDB complex is only reported or cited in the paper, normally without specifying further details.
    • Comments
      Comments and additional valuable information regarding the method, the reference, or the affinity value itself may be found here.

    III. Tabluar reports
    Tabular reports are used for displaying search results and for general browsing through the database. Tables are created only for PDB entries with available affinity data. The format consists of six columns providing the following information:
    • a drawing of the Ligand structure;
    • the PDB code, linked to the summary information for the PDB entry;
    • the Affinity value, provided in the originally reported form as well as converted to the negative base-10 logarithm (e.g., Kd and pKd); Ka and ΔG values are converted to Kd and hence to pKd values. A link to the affinity information window is also available. (Please note that all values are given here with two decimal places of precision; this does not reflect the actual precision of the experimental value!);
    • the pH value of the measurement, if reported in the reference;
    • the first Author of the publication refering the affinity value;
    • the Year of the publication.
    Tables reporting search results may be sorted by the values in any of the following columns: PDB, Affinity, pH, Author, Year, and Molecular Weight of the ligand (if part of the search query). To sort a table, simply click on the corresponding column header. To reverse the sorting order, click on the same column header again.
    Tables reporting search results can be saved as 'csv' file using the link in the top right corner of the table. The csv file is an ASCII file with semicolon-separated columns and one affinity entry per line (with the column headers in the first line). For each affinity entry, the following information (if available) is provided in one line:
    • Ligand Name;
    • Molecular Weight (of the ligand; provided only if part of the query);
    • PDBcode;
    • Affinity;
    • Unit (this is the unit of the affinity value, e.g. nM);
    • Error (this is the experimental uncertainty);
    • Measurand (this is the type of affinity value, e.g. Ki);
    • Affinity log10 (this is the negative base-10 logarithm of the affinity value; for Ka and ΔG after conversion to Kd);
    • pH;
    • Temperatur;
    The entries in the csv file are not sorted. Also, please note that in the csv file a comma is used instead of a decimal point.

  7. Searching and Browsing the Database
  8. Data of the Affinity Database are accessible through the PDB code, by defining specific search queries using the affinity search form, or simply by browsing.

    Access by PDB code
    On the left navigation bar of the main window, a data entry field is available for specifying a PDB code (case insensitive). If a valid code corresponding to an actual PDB entry is entered, the summary information for the PDB entry is shown, which is independent of the presence of an affinity value. In contrast, searching for a specific PDB entry with the affinity search form yields only a result if an affinity value is already associated with the corresponding PDB entry.

    Searching the database using the affinity search form
    The 'Search' button in the top and left navigation bar of the main window opens the affinity search form. Here, a variety of search queries for affinity data and related information can be defined. It is possible to search for affinities of a certain magnitude and for measurements carried out at a specific temperature or pH range. Affinities for certain enzyme classes or a specified PDB code may be retrieved, as well as affinities for ligands of a certain molecular weight range. Also the affinity values published by a certain author or within a specified time frame can be requested, and the retrieved affinity values may be limited to those obtained from primary literature sources.

    More in detail, the following search fields are available:
    • Affinity data: to retrieve affinity values of a specific magnitude (field 'exact') or within a certain range. If only one value is entered in the range fields leaving the other one empty, the search will retrieve all values starting from (left field filled) or leading up to (right field filled) this value; this applies also to all other range fields in the search form.
      The values must be specified as negative base-10 logarithms (i.e., as pKi, pKd, or pIC50). The search can be limited to pKi, pKd and/or pIC50 values. Ka and ΔG values are internally converted to Kd and hence to pKd values. Accordingly, searching for pKd data will also retrieve values reported as Ka or ΔG.
    • Temperature: to retrieve affinity data measured at a certain temperature (field 'exact') or within a certain temperature range.
    • pH: to retrieve affinity data measured at a certain pH (field 'exact') or within a certain temperature range.
    • E.C. Number: to retrieve affinity data measured for a certain enzyme class. The search may be defined for any E.C. level, i.e., either as (for example) 3.4.21.5 or 3.4.21.* or 3.4.* or 3.* . Please note that currently not all PDB enzyme structures in the database have their E.C. number assigned.
    • PDB Code: to retrieve affinity data measured for a certain PDB complex. '*' is allowed as wildcard.
    • Molecular Weight: to retrieve affinity data measured for ligands within a certain range of molecular weight. If and only if this criterium is included in the search query, the molecular weight is shown in the tabluar report of the search results which can be saved as csv file.
    • Author name: to retrieve affinity data published by a certain author. Only the first author of the affinity publications is stored in the database.
    • Year: to retrieve affinity data published in a certain year (field 'exact') or within a certain time frame (field 'range').
    • Primary Literature: check this box to retrieve affinity values obtained from primary literature sources only.

    Search queries using criteria from more than one of these fields at the same time will retrieve affinity entries satisfying all of the requested criteria.
    The results are displayed as tabular report and may be saved as csv file. Please note again that the molecular weight is only included in the table if the search query contained a molecular-weight criterium.

    Browsing the database
    The 'Browse' button in the top and left navigation bar of the main window opens a tabular report of all available affinity data. By default, 20 entries are shown per page. The number of entries shown per page can be modified by the user. Buttons for scrolling back and forth are available at the beginning and the end of the displayed page. The entries in the table are sorted by PDB code (alphanumerically ascending).

    The latest entries to the database are accessible by following the corresponding link in the left navigation bar of the main window. It leads to a tabular report of the last 15 affinity additions to the database. This table may also be saved as a csv file.

  9. Adding New Data
  10. Database users are encouraged to notify the administrators about any valuable publication which reports affinity data for PDB complexes. Please use the contact form for this purpose.

    Direct addition of new data to the database is only possible for registered users. Scientists interested in supporting the further growth of the database by adding data should contact the administrators of the database.

  11. Acknowledgement and Disclaimer
  12. Special thanks are due to Dr. Ingo Dramburg for technical support in the very early stages of the database development. The help of the following students in collecting and processing literature data is gratefully acknowledged: Kathrin Austrup, Petra Cordes, Julia Engel, Silvia Funke, Steffen Hoefft, Stefanie Meseth, Birte Roessing, Sebastian Vollmer.

    The developers have taken all reasonable care to ensure that the data provided by AffinDB accurately reflect the original data provided in the corresponding publications and databases. However, it cannot be entirely ruled out that errors may occur. If you observe any potential errors or bugs, please report your observations and suggestions by means of the contact form. No responsibility for the consequences of any errors in the database or in the data incorporated into the database is taken. Use of the information provided on any of the AffinDB pages does not form any basis of a contract with the developers or providers of the database. Likewise, no warranties or liabilities are expressed or implied in the supply of the database.

  13. References
  14. All 2D ligand depictions were created using Openeye Babel/OpenBabel and Chemaxon Marvin Molconvert.