Wrap 'n' Shake (WnS) consists of Wrapper and Shaker steps. Wrapper builds a monolayer of ligand copies around the target molecule. Shaker removes loosely bound ligand copies from the surface of the target using molecular dynamics. WnS is a useful tool of fast and systematic prediction of multiple binding modes at atomic resolution. WnS combines the advantages of available open source program packages AutoDock 4.2.3 and GROMACS for efficient and reliable blind docking
Wrapper performs automated, fast blind docking cycles. The algorithm ensures a complete and systematic coverage of the surface of the target with ligand copies. Wrapper uses a modified docking force field and clustering allowing maximal ligand-target and minimal ligand-ligand interactions. The popular docking program AutoDock 4.2.3 is piped into Wrapper and performs consecutive fast blind docking cycles without the need of starting ligand positions or any other interventions of the user. The outcome of Wrapper is a single Protein Databank file including the structure of the wrapped target, i.e. the target-ligandN complex
Shaker challenges the wrapped target using dissociation in molecular dynamics (MD) simulations with explicit water molecules. The wrapped target is placed in a simulation box and hydrated with explicit water molecules (I). The hydrated complex is subjected to a series of simulations including MD with position restraints on target backbone and simulated annealing (II). There are filtering steps between the MD runs, where loosely bound ligand copies are removed. Clustering and ranking provides the final solution as a single Protein Databank file with the structure of representative ligand copies bound to the target (III). In a final step, refinement of bound ligand structure is performed with all target atoms released. The use of explicit water molecules and a released target increase efficiency and precision