1. Target definition
All tools in the ProteinsPlus server work on a structure of a
protein or a nucleic acid. In the first step, you need to define this structure either
by selecting a structure form the Protein Data Bank (PDB) via its PDB code (e.g. 1a99)
or upload any other structure in PDB format. Additional ligand molecules can be provided
in SDF format.
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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 Structure visualization for 3D query selection
GeoMine performs textual, numerical and 3D searches with full chemical
awareness in protein-ligand pockets of the entire PDB dataset. Prepare the visualization
in the 3D viewer to facilitate the 3D query creation: E.g. select and focus a
precalculated pocket entry from the "Pockets" tab on
the left, set all "Representation Options" below the 3D viewer to "Off",
hide the "Ligands"/"Pockets" tab and set the background to "White".
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
protein-ligand complex, e.g. the enzyme class or the hydrophobicity of a pocket.
All search types can be used independently or in combination.
Press "Search" in any of the query tabs to start the GeoMine search.
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4.1 3D query selection
The interactive 3D panel allows the generation of queries from scratch and based on
the 3D representation of an existing protein-ligand complex or
its pockets. You can select the 3D query in any
structure, the most convenient way is to select it
in a precalculated pocket from the "Pockets" tab.
The precalculated pockets were processed by Protoss and GeoMine.
They contain water molecules, ions, ligands, other small molecules and interactions:
H-Bond (blue), Ionic (magenta), Metal (yellow), Pi-Cation (green), Pi-Pi (cyan).
Furthermore, selectable GeoMine features like aromatic ring centers are visualized.
The template structures can be switched on and off.
The 3D query is visualized in the 3D viewer and
in tables for further modification of chemical and geometrical properties.
Main properties like the element name of a point are automatically set.
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4.2 3D query selection
Choose a selection mode in order to select a 3D query in the 3D viewer.
Define points by clicking on atoms
and aromatic ring centers. Generic points can be added clicking on an
unoccupied point in the 3D viewer. These points can
subsequently be translated in the 3D viewer
to the desired position if the point is not connected by point-point constraints.
The selected points can be further specified by different attributes.
Point-point constraints (distances and interactions)
can be defined by clicking on a pair of points.
They can also be added directly by clicking on atoms and aromatic ring centers.
The corresponding points are automatically added.
Angle constraints can be defined between connected point-point
constraints clicking on these two. Also ring normals of aromatic ring centers
can be used for angle definition. Hide the precalculated pocket in order to facilitate
the definition of point-point constraints and angles between already set points.
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5. Textual / numerical property filter selection
The numerical and textual properties can be added to a table. The filters
can be negated and a PDB must fulfill all defined filters to be a match. For the
textual filters, a list of properties can be defined. Here a matching PDB must fulfill
only one of these properties. You can inspect a filter 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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6. XML query
The currently selected query can be converted
to XML which can then be used for the REST API.
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7. Result
An search process of successive query modifications and
result analyses can be made using the refinement functionality.
The results can be refined continuing the search in the results
and with the current 3D query as a new starting point.
GeoMine produces a list of all matching PDBs.
The first 150 results can be displayed as superimpositions onto the 3D query in the viewer
for visual analysis with different representation options. Besides the visual analysis
of the hits, their pockets can be downloaded as .pdb files and common structural
aspects of all results can be inspected with a statistics report.
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your results later, you can copy a link to the results.
