Receptor ensemble docking

Fig. 8. The accuracy of the ligand binding pose prediction for different ensemble sizes. The tors reflect the fraction of the ligands that dock correctly using traditional ensemble docking and 4D docking for varying ensemble size, compared to the accuracy of a single-receptor cross-docking.

Because the receptor conformations are changed concurrently with the ligand conformations, a 4D simulation convergence time is comparable with that of a single receptor docking, and is significantly shorter than for the traditional ensemble docking ... 

Fig. 9. Unlike the traditional ensemble docking, the 4D protocol docks the ligand into a set of receptor conformations in a single docking run.

Aldose reductase DOCK [40] Receptor ensemble-based docking Discovery of new ligands Low/mid pM [55]... 

Docking to multiple receptor conformations (sometimes abbreviated MRC [8]) can be applied on a set of conformations from any source. Experimentally different X-ray conformations or NMR solution stmctures can represent the same biomolecular system. NMR solution stmctures and conformations sampled during an MD simulation represent a valid thermodynamic ensemble, e.g., a canonical ensemble, for simulations with constant number of particles, volume, and temperature. Although, a collection of X-ray stmctures is not a valid thermodynamic ensemble, docking to multiple X-ray stmctures is sometimes also termed ensemble docking. 

Fig. 15.3 We classify the approaches to represent an MD tiqectory for the subsequent molecular docking into five alternative strategies merged structure representation, periodic structure selection, selection of structures based on a clustering, guided by the performance of individual structures, or selection of structures during docking. Subsequent molecular docking relies on chosen the receptor ensemble representation...

Bolstad ES, Anderson AC (2009) In pursuit of virtual lead optimization pruning ensembles of receptor structures for increased efficiency and accuracy during docking. Proteins 75(l) 62-74... 

Recently, the importance of generating inhibitors that target receptor conformational ensembles has been pointed out (10). This method goes beyond the current docking of knovm structures to known active site con-formers and can lead to type III and GRAB peptidomimetics. 

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