SpaceHASTEN: A structure-based virtual screening tool for non-enumerated virtual chemical libraries

Given the size of the drug discovery relevant chemical space, working with fully enumerated compound libraries (especially in 3D) is unfeasible. Non-enumerated virtual chemical spaces are a practical solution to this issue; where compounds are described as building blocks which are then connected by rules. One concrete example of such is the BioSolveIT chemical spaces file format (.space). Tools to search these space-files exist that are using ligand-based methods including, 2D fingerprint similarity, substructure matching, and fuzzier similarity metrics such as FTrees. However, there is no software available that enables the screening of these spaces using molecular docking. Here, a tool, called SpaceHASTEN, was developed on top of SpaceLight, FTrees, LigPrep, and Glide to allow efficient virtual screening of nonenumerated chemical spaces. SpaceHASTEN was validated using three public targets picked from the DUD-E dataset. It was able to retrieve a large number of diverse and novel high scoring compounds (virtual hits) from non-enumerated chemical spaces of billions of molecules, after docking a few million compounds. The software can be freely used and is available from http://github.com/TuomoKalliokoski/SpaceHASTEN. Keywords: