van Hilten N, Chevillard F, Kolb P (2019) Virtual compound libraries in computer-assisted drug discovery. J Chem Inform Modeling 59:644–651

Article  Google Scholar 

Walters WP (2018) Virtual chemical libraries: miniperspective. J Med Chem 62:1116–1124

Article  PubMed  Google Scholar 

Chevillard F, Kolb P (2015) SCUBIDOO: a large yet screenable and easily searchable database of computationally created chemical compounds optimized toward high likelihood of synthetic tractability. J Chem Inform Modeling 55:1824–1835

Article  CAS  Google Scholar 

Humbeck L, Weigang S, Schäfer T, Mutzel P, Koch O (2018) CHIPMUNK: a virtual synthesizable small-molecule library for medicinal chemistry, exploitable protein-protein interaction modulators. ChemMedChem 13:532–539

Article  PubMed  CAS  Google Scholar 

Korn M, Ehrt C, Ruggiu F, Gastreich M, Rarey M (2023) Navigating large chemical spaces in early-phase drug discovery. Curr Opin Struct Biol 80:102578

Article  PubMed  CAS  Google Scholar 

Warr WA, Nicklaus MC, Nicolaou CA, Rarey M (2022) Exploration of ultralarge compound collections for drug discovery. J Chem Inform Modeling 62:2021–2034

Article  CAS  Google Scholar 

Hoffmann T, Gastreich M (2019) The next level in chemical space navigation: going far beyond enumerable compound libraries. Drug Discov Today 24:1148–1156

Article  PubMed  CAS  Google Scholar 

Klingler F-M, Gastreich M, Grygorenko OO, Savych O, Borysko P, Griniukova A, Gubina KE, Lemmen C, Moroz YS (2019) SAR by space: enriching hit sets from the chemical space. Molecules 24:3096

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chevillard F, Rimmer H, Betti C, Pardon E, Ballet S, van Hilten N, Steyaert J, Diederich WE, Kolb P (2018) Binding-site compatible fragment growing applied to the design of \(\beta\)2-adrenergic receptor ligands. J Med Chem 61:1118–1129

Article  PubMed  CAS  Google Scholar 

Virshup AM, Contreras-García J, Wipf P, Yang W, Beratan DN (2013) Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds. J Am Chem Soc 135:7296–7303

Article  PubMed  PubMed Central  CAS  Google Scholar 

van Deursen R, Reymond J-L (2007) Chemical space travel. ChemMedChem: Chem Enabling Drug Discov 2:636–640

Article  Google Scholar 

Detering C, Claussen H, Gastreich M, Lemmen C (2010) KnowledgeSpace-a publicly available virtual chemistry space. J Cheminform 2:1–1

Article  Google Scholar 

Hu Q, Peng Z, Kostrowicki J, Kuki A (2011) LEAP into the Pfizer Global Virtual Library (PGVL) space: creation of readily synthesizable design ideas automatically. Chem Lib Design. https://doi.org/10.1007/978-1-60761-931-4_13

Article  Google Scholar 

Nicolaou CA, Watson IA, Hu H, Wang J (2016) The proximal lilly collection: mapping, exploring and exploiting feasible chemical space. J Chem Inform Modeling 56:1253–1266

Article  CAS  Google Scholar 

Boehm M, Wu T-Y, Claussen H, Lemmen C (2008) Similarity searching and scaffold hopping in synthetically accessible combinatorial chemistry spaces. J Med Chem 51:2468–2480

Article  PubMed  CAS  Google Scholar 

Lessel U, Wellenzohn B, Lilienthal M, Claussen H (2009) Searching fragment spaces with feature trees. J Chem Inform Modeling 49:270–279

Article  CAS  Google Scholar 

Warr W. Report on an NIH workshop on ultralarge chemistry databases. 2021,

(2023)Enamine, Enamine REAL Space. https://enamine.net/compound-collections/real-compounds/real-space-navigator, accessed on November 01

WuXi LabNetwork, GalaXi Space. https://www.labnetwork.com/frontend-app/p/#!/library/virtual, accessed on November 01, (2023)

OTAVAchemicals, CHEMriya Space. https://www.otavachemicals.com/products/chemriya, accessed on November 01, (2023)

Neumann A, Marrison L, Klein R (2023) Relevance of the trillion-sized chemical space “eXplore’’ as a source for drug discovery. ACS Med Chem Lett 14:466–472

Article  PubMed  CAS  Google Scholar 

Chemspace, Freedom Space. https://chem-space.com/compounds/freedom-space, accessed on November 01, (2023)

Pottel J, Moitessier N (2017) Customizable generation of synthetically accessible, local chemical subspaces. J Chem Inform Modeling 57:454–467

Article  CAS  Google Scholar 

Zabolotna Y, Volochnyuk DM, Ryabukhin SV, Gavrylenko K, Horvath D, Klimchuk O, Oksiuta O, Marcou G, Varnek A (2021) SynthI: a new open-source tool for synthon-based library design. J Chem Inform Modeling 62:2151–2163

Article  Google Scholar 

Wahl J, Sander T (2022) Fully automated creation of virtual chemical fragment spaces using the open-source library OpenChemLib. J Chem Inform Modeling 62:2202–2211

Article  CAS  Google Scholar 

Fischer JR, Lessel U, Rarey M (2011) Improving similarity-driven library design: customized matching and regioselective feature trees. J Chem Inform Modeling 51:2156–2163

Article  CAS  Google Scholar 

Brown N (2013). Feature Trees. https://doi.org/10.1002/9783527665143.ch09

Article  Google Scholar 

Bellmann L, Penner P, Rarey M (2020) Topological similarity search in large combinatorial fragment spaces. J Chem Inform Modeling 61:238–251

Article  Google Scholar 

Schmidt R, Klein R, Rarey M (2021) Maximum common substructure searching in combinatorial make-on-demand compound spaces. J Chem Inform Modeling 62:2133–2150

Article  Google Scholar 

Degen J, Rarey M (2006) FlexNovo: structure-based searching in large fragment spaces. ChemMedChem: Chem Enabling Drug Discov 1:854–868

Article  CAS  Google Scholar 

Sadybekov AA et al (2022) Synthon-based ligand discovery in virtual libraries of over 11 billion compounds. Nature 601:452–459

Article  ADS  PubMed  CAS  Google Scholar 

Muller J et al (2022) Magnet for the needle in haystack: crystal structure first Fragment hits unlock active chemical matter using targeted exploration of vast chemical spaces. J Med Chem 65:15663–15678

Article  PubMed  Google Scholar 

Beroza P, Crawford JJ, Ganichkin O, Gendelev L, Harris SF, Klein R, Miu A, Steinbacher S, Klingler F-M, Lemmen C (2022) Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors. Nat Commun 13:6447

Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

Meyenburg C, Dolfus U, Briem H, Rarey M (2023) Galileo: three-dimensional searching in large combinatorial fragment spaces on the example of pharmacophores. J Comput-Aided Mole Design 37:1–16

Article  ADS  CAS  Google Scholar 

Hönig SM, Lemmen C, Rarey M (2023) Small molecule superposition: a comprehensive overview on pose scoring of the latest methods. Wiley Interdiscip Rev: Comput Mole Sci 13:e1640

Google Scholar 

Grant JA, Gallardo MA, Pickup BT (1996) A fast method of molecular shape comparison: a simple application of a Gaussian description of molecular shape. J Comput Chem 17:1653–1666

Article  CAS  Google Scholar 

Open Eye Scientific Software, Santa Fe, NM, ROCS. 2006; https://www.eyesopen.com/rocs, accessed on November 28, (2023)

Lemmen C, Lengauer T, Klebe G (1998) FlexS: a method for fast flexible ligand superposition. J Med Chem 41:4502–4520

Article  PubMed  CAS  Google Scholar 

Lemmen C, Lengauer T (1997) Time-efficient flexible superposition of medium-sized molecules. J Comput-Aided Mole Design 11:357–368

Article  ADS  CAS  Google Scholar 

FlexS Version 5.0.0, BioSolveIT GmbH, St. Augustin, Germany, (2023), biosolveit.de/FlexS

Chan SL, Labute P (2010) Training a scoring function for the alignment of small molecules. J Chem Inform modeling 50:1724–1735

Article  CAS  Google Scholar 

Molecular Operating Environment (MOE). https://www.chemcomp.com/Products.htm, accessed on November 28, 2023

FastROCS Toolkit | Real-Time Shape Similarity | Lead Discovery. https://www.eyesopen.com/molecular-modeling-fastrocs, accessed on November 28, 2023

Penner P, Martiny V, Gohier A, Gastreich M, Ducrot P, Brown D, Rarey M (2020) Shape-based descriptors for efficient structure-based fragment growing. J Chem Inform Modeling 60:6269–6281

Article  CAS  Google Scholar 

Penner P, Martiny V, Bellmann L, Flachsenberg F, Gastreich M, Theret I, Meyer C, Rarey M (2022) FastGrow: on-the-fly growing and its application to DYRK1A. J Comput -Aided Mole Design 36:639–651

Article  ADS  CAS  Google Scholar 

Wang R, Fang X, Lu Y, Wang S (2004) The PDBbind database: collection of binding affinities for protein- ligand complexes with known three-dimensional structures. J Med Chem 47:2977–2980

Article  PubMed  CAS  Google Scholar 

Wang R, Fang X, Lu Y, Yang C-Y, Wang S (2005) The PDBbind database: methodologies and updates. J Med Chem 48:4111–4119

Article  PubMed  CAS  Google Scholar 

Hu J, Liu Z, Yu D-J, Zhang Y (2018) LS-align: an atom-level, flexible ligand structural alignment algorithm for high-throughput virtual screening. Bioinformatics 34:2209–2218

Article