FlexX is one of the most established protein-ligand docking tools in the literature. Cited hundreds of times, it has proved to be highly successful in numerous. register. BioSolveIT. expect actives! docking with molecular template superposition. home · products · SeeSAR; structure-based. docking / FlexX · scoring / HYDE. In order to assesses the docking accuracy and mode of binding, initially, FlexX was evaluated on a set of 19 protein–ligand complexes, with a.
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FlexX can superimpose a part of a ligand-to-dock onto a known crystal structure of a ligand. The “template ligand” may, for example, be known to bind within a specific active site in a very specific manner, rocking the modeler wants to ensure that this knowledge is pertained in a docking protocol.
Another application to be thought of is side-chain docking of a series of highly similar compounds:. The overall core and ligand structures have to be very similar for mapping to occur correctly, small differences in bond and atom types can be tolerated.
Firstly, the ligand to be docked needs to be read into FlexX as normal:. Then the MAPREF command can be used to map the desired dockibg to a core reference structure known to be in the active site:.
In the example we provide below, a template is provided, dicking.
The options following the filename input of the core are, for checking bond type matches, checking atom type matches, and whether to include hydrogen atoms, respectively. Symmetrical ligand fragments may have the problem of aligning in a flipped way. For such mappings to occur correctly molecules need an individual distinctive R dockign as a discrete point for mapping as FlexX will not know where to place the next ligand fragment.
For example, in the picture below the sulfur atom linked to the heterocyclic ring provides this:. When a ligand is read with the READ command with default initialization settings, FlexX will try to prepare “initialize” the ligand with respect to aromaticity, protonation, charges, atom types, bond types etc.
This process may change your input ligand so that atom types and bond types may not match flex anymore and no mappings will be found with MAPREF.
BioSolveIT GmbH – FlexX: installation
The 10 refers to atom typing, see the FlexX manual for further details. Now the base selection, the first fragment to be selected for placement in the binding dcking, should be undertaken with the SELBAS command and an ‘ r ‘ or ‘ f ‘ flag.
The ‘ r ‘ flag, reference mode, uses the superimposed co-ordinates of the ligand from the input template obtained from MAPREF. Multiple conformations are mapped and can be selected from MAPREF due to any torsion bonds found within a base fragment.
BioSolveIT GmbH – tips & tricks: docking with molecular template superposition
Alternatively the ‘ f ‘ flag can be used. This is a freeze mode which takes the conformation of the base fragment as the frozen conformation of the reference structure. Therefore, exactly the same placement as given in doccking reference structure will be flesx. Using a ‘ p ‘ flag will trigger the perturbation mode dockong the base fragment is manually placed onto the core reference coordinates; however, instead of the single reference orientation of the base, the ligand fragment is perturbated such that a set of slightly different placements is generated which increases the probability of success for docking.
An increase in success is obtained as small differences in the vital step of placing the first fragment may have large implications as the ligand is incrementally built.
At this point, you can check how FlexX placed your initial fragment:. For your convenience, an example zip file is linked here.