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FlexX-Ensemble (formerly known as FlexE) is an extension module of FlexX that is able to take protein flexibility into account. FlexX-Ensemble predicts not only the binding mode of a ligand, but also combines a suitable protein conformation from a set of given protein structures on the fly.
The two main applications of FlexX-Ensemble are complex prediction and virtual screening. You can carry out complex prediction when you have a protein and a small molecule binding to it but no structure of the protein-ligand complex. FlexX-Ensemble can then be used to create and rank a series of possible protein-ligand complexes. For virtual screening, you have a protein and a set of compounds and you are interested in prioritizing the compounds for experimental testing.
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| features |
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The conformational flexibility of the protein is considered. The flexibility of the protein is represented by an ensemble of protein structures which is combined to a so-called united protein description. |
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FlexX-Ensemble is able to recombine elements from different ensemble structure to new valid protein structures. Thus, FlexX-Ensemble is able to take a larger conformational space into account than given by the particular ensemble structures. Using graph search algorithms, the optimal combination of ensemble structures is determined for each ligand. |
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The conformational flexibility of the ligand is considered. Torsion angle flexibility as well as the conformational flexibility of ring systems is taken into account. In addition, enantiomerism can be handled as a degree of freedom which is important in cases where the set of compounds are automatically created from a 2D database. |
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FlexX-Ensemble is fast. On our benchmark set of ten ensembles containing 106 protein structures and 60 ligands, FlexX-Ensemble takes about 5 minutes per complex prediction on average. The computing time depends on the number of protein ensemble structures, the flexibility of the protein, size of the active site, the size of the ligand, and the degree of ligand symmetry and lies in the range from a few seconds up to a few minutes. |
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The placement algorithm in FlexX-Ensemble is based on the evaluation of interactions occurring between the molecules. This ensures that the search is limited to low-energy structures improving the quality of the results in a given amount of computing time. |
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FlexX-Ensemble is based on sophisticated physico-chemical models. The MIMUMBA torsion angle database is used for the creation of conformers, an interaction geometry database is used to exactly describe intermolecular interaction patterns. For scoring, the Boehm function (with minor adaptions necessary for docking) is applied. |
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| status & availability |
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FlexX-Ensemble is available as a modular extension of FlexX. In order to use FlexX-Ensemble an additional license key is necessary.
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m this link leads back to mother tool FlexX |
