2. Tool selection

Afterwards you can select the tool you are interested in. You can choose GeoMine either by selecting it from the drop-down menu or by following the link under the respective tool description.
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3. Set up 3D query selection

GeoMine performs textual, numerical, chemical and 3D searches in ligand-based and empty pockets of the entire PDB dataset. Possible use cases are the search for ligands for a given pocket or off-targets for a given ligand. You can select a 3D query in a 3D pocket or 2D ligand interaction diagram or both since the 2D and 3D viewer are synchronized. You can also create a 3D query partially or completely from scratch.
The 2D ligand interaction diagrams are drawn by PoseEdit. The 3D pockets are processed by Protoss, DoGSiteScorer and GeoMine. Empty pockets with a volume less than 100 cubic angstrom are excluded and their number is limited to twice the number of chains. If DogSite could not calculate a pocket for a ligand, the radius pocket (6.5 angstrom) of the ligand is added. If DogSite could not calculate a pocket for a ligand, the radius pocket (6.5 angstrom) of the ligand is added. Empty pockets with a volume less than 100 cubic angstrom are excluded and their number is limited to twice the number of chains.

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4.1 3D query selection

The 3D pockets contain water molecules, ions, ligands, other small molecules and interactions of the following types: hydrogen bond, ionic, metal, pi-Cation and pi-pi interactions. Furthermore, GeoMine features that are selectable for the 3D query (binding site surface atoms, aromatic ring centers and normals, end/mid alpha carbon atoms and directions of helices and strands) are visualized.
Note, that a 2D ligand interaction diagram is only an excerpt of the corresponding 3D pocket being focused on the interactions of a specific ligand with residues and metals of the binding site.
Choose a selection mode in order to select a 3D query in the 2D/3D viewer.
Point: Define points by clicking on (surface) atoms and aromatic ring centers or secondary structure elements (mid/end alpha carbon atoms). Surface atoms are represented by non transparent big spheres. Undefined points can be added clicking on an unoccupied position in the 3D viewer. These points can subsequently be translated in the 2D/3D viewer to the desired position, if the point is not connected by a distance or interaction. In order to specify an undefined point as aromatic ring center, its 'Element' must be set to 'Any' and its 'Type' to 'Aromatic Ring Center'. Points can be further specified by different attributes.
Distance/Interaction: Point-point constraints can be defined by clicking on a pair of points. They can also be added directly by clicking on atoms, aromatic ring centers, secondary structure elements and interactions. The corresponding points are automatically added. The interaction type (e.g. Ionic) and point types (e.g. Cation/Anion) will be automatically set, if an interaction is available between the points. The default distance tolerance value is 0.5 A.
Angle: Angle constraints can be defined between connected point-point constraints clicking on these two. Also ring normals of aromatic ring centers and directions of secondary structure features can be used for angle definition. The default angle tolerance is 15 degree.
The selected 3D query is loaded in tables for the inspection and further modification of its chemical and geometrical properties. Regarding the 'Point' selection mode, main properties of a point like the chemical element of an atom are automatically set. You can specify that more discriminative point properties are automatically set by marking the checkbox next to the selection mode dropdown. Note that for a valid 3D query, all points must be part of at least one selected distance or interaction. Besides the 3D query, a GeoMine search might also contain a PDB subselection, which restricts the search to a user-defined set of PDB codes, and filters for textual/numerical properties of any component of the PDB, e.g. the enzyme class or the hydrophobicity of a pocket. All query types can be used independently or in combination.
Click 'Search' in any of the query tabs to start the GeoMine search.
Click 'Export query/Import query' for saving and reloading a GeoMine query
Click 'Rest-service XML' for saving a query as XML usable by the GeoMine REST-serivce.

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4.2 3D query selection

5. Textual/numerical property filter selection

Textual and numerical properties can be added to a table. The filters can be negated and all defined filters have to be fulfilled for a match. For the textual filters, a list of properties can be defined. Here a match must fulfill only one of these properties. You can inspect a description of the filter that is currently selected in the dropdown by hovering over the info icon next to it.

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6. PDB codes selection

Put PDB codes (case insensitive) into the respective text box to limit the search on a PDB subselection. Please separate the PDB codes by newlines. If the text box is empty, the complete database will be searched. Using the result refinement feature, all resulting PDB codes that matched the search criteria are loaded into this text box for further refinement of the search and results.

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7. Result

An search process of successive query modifications and result analyses can be performed using the refinement and history functionality. The results can be refined continuing the search in all found PDB codes and with the current 3D query as a new starting point. The results history allows browsing through prior and successive search results obtained by refinement.
Visualizable results are presented in the results table. They can be displayed in the 3D viewer individually or together as superimpositions for visual analysis with different representation options. The number of visualizable results is limited to 150, the downloadable search statistic report however includes all detected results. If the search contains a 3D query, the results table is initially sorted by RMSD. The RMSD is calculated considering the 3D query points and the respective result points that match the 3D query points.
The table can be searched, e.g. with respect to the PDB title, and its entries sorted, e.g. by their enzyme classes. Besides the visual analysis of hits, a search statistics report containing common structural aspects of the complete results list as well as the pocket .pdb files and the table content as .json and .csv files of the 150 visualizable results can be downloaded.
If you want to access your results later (max 30 days), you can copy a link to the results.

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