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ZBHCenter for Bioinformatics

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SpaceGrow Dataset

A navigation through reaction-driven combinatorial libraries, so-called chemical spaces, offers synthetically accessible compounds far beyond the reach of enumerable databases. The SpaceGrow dataset [1] was compiled for 3D shape-based virtual screening applications to compare approaches for searching in chemical spaces to conventional approaches searching in enumerable databases. The dataset comprises 160 ligands picked from a list of known drugs [2] which were found in PDBbind structures [3]. For 56 ligands selected as references, ligands binding in the same active site were superimposed with respect to their native binding mode [4] to form homologous ligand pairs. Both ligands of each pair were fragmented into a chemical space, the validation space, by cutting all acyclic bonds. Enumerating all molecules, the validation library contains 34 134 molecules. The validation space and library are included in the dataset and can be used to benchmark tools regarding the rank and RMSD with which the binding pose of the reference ligand is reproduced. Furthermore, searching the reference ligand, the rank and RMSD of the homologous ligand pose can be evaluated.

People and References

[1] Hönig, S. M. N.; Flachsenberg, F.; Ehrt, C.; Neumann, A.;Schmidt, R.; Lemmen, C.; Rarey, M. (2024) SpaceGrow: Efficient Shape-based Virtual Screening of Billion-sized Combinatorial Fragment Spaces. Journal of Computer Aided Molecular Design, doi: 10.1007/s10822-024-00551-7

[2] Neumann, A.; Marrison, L.; Klein, R. Relevance of the trillion-sized chemical space “eXplore” as a source for drug discovery. ACS Medicinal Chemistry Letters 2023, 14, 466–472

[3] Wang, R.; Fang, X.; Lu, Y.; Wang, S. The PDBbind database: Collection of binding affinities for protein- ligand complexes with known three-dimensional structures. Journal of medicinal chemistry 2004, 47, 2977–2980

[4] Bietz, S.; Rarey, M. (2016) SIENA: Efficient Compilation of Selective Protein Binding Site Ensembles . Journal of Chemical Information and Modeling, 56(1):248-59. ()