{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:39:46Z","timestamp":1792136386564,"version":"4.4.0"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Structure-based fragment growing is one of the key techniques in fragment-based drug design. Fragment growing is commonly practiced based on structural and biophysical data. Computational workflows are employed to predict which fragment elaborations could lead to high-affinity binders. Several such workflows exist but many are designed to be long running noninteractive systems. Shape-based descriptors have been proven to be fast and perform well at virtual-screening tasks. They could, therefore, be applied to the fragment-growing problem to enable an interactive fragment-growing workflow. In this work, we describe and analyze the use of specific shape-based directional descriptors for the task of fragment growing. The performance of these descriptors that we call ray volume matrices (RVMs) is evaluated on two data sets containing protein\u2013ligand complexes. While the first set focuses on self-growing, the second measures practical performance in a cross-growing scenario. The runtime of screenings using RVMs as well as their robustness to three dimensional perturbations is also investigated. Overall, it can be shown that RVMs are useful to prefilter fragment candidates. For up to 84% of the 3299 generated self-growing cases and for up to 66% of the 326 generated cross-growing cases, RVMs could create poses with less than 2 \u00c5 root-mean-square deviation to the crystal structure with average query speeds of around 30,000 conformations per second. This opens the door for fast explorative screenings of fragment libraries.<\/jats:p>","DOI":"10.1021\/acs.jcim.0c00920","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T09:34:42Z","timestamp":1605519282000},"page":"6269-6281","source":"Crossref","is-referenced-by-count":12,"title":["Shape-Based Descriptors for Efficient Structure-Based\nFragment Growing"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4988-6183","authenticated-orcid":true,"given":"Patrick","family":"Penner","sequence":"first","affiliation":[{"name":"Universita\u0308t Hamburg , , Bundesstr. 43 , ,","place":["Hamburg, Germany, 20146"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Martiny","sequence":"additional","affiliation":[{"name":"Institut Recherches de Servier , 125 Chemin de Ronde , ,","place":["Croissy, France, 78290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Gohier","sequence":"additional","affiliation":[{"name":"Institut Recherches de Servier , 125 Chemin de Ronde , ,","place":["Croissy, France, 78290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Gastreich","sequence":"additional","affiliation":[{"name":"BioSolveIT GmbH , An der Ziegelei 79 , ,","place":["Sankt\nAugustin, Germany, 53757"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Ducrot","sequence":"additional","affiliation":[{"name":"Institut Recherches de Servier , 125 Chemin de Ronde , ,","place":["Croissy, France, 78290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brown","sequence":"additional","affiliation":[{"name":"Institut Recherches de Servier , 125 Chemin de Ronde , ,","place":["Croissy, France, 78290"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-6531","authenticated-orcid":true,"given":"Matthias","family":"Rarey","sequence":"additional","affiliation":[{"name":"Universita\u0308t Hamburg , , Bundesstr. 43 , ,","place":["Hamburg, Germany, 20146"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"2026081804404452400_cit1","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nrd.2016.109","article-title":"Twenty years\non: the impact of fragments on drug discovery","volume":"15","author":"Erlanson","year":"2016","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026081804404452400_cit2","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrd2220","article-title":"A decade of fragment-based\ndrug design: Strategic advances and lessons\nlearned","volume":"6","author":"Hajduk","year":"2007","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026081804404452400_cit3","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1002\/anie.200462457","article-title":"Virtual Exploration of the Small-Molecule\nChemical Universe below 160 Daltons","volume":"44","author":"Fink","year":"2005","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026081804404452400_cit4","doi-asserted-by":"publisher","first-page":"751","DOI":"10.2174\/1568026054637700","article-title":"Library design\nfor fragment based screening","volume":"5","author":"Schuffenhauer","year":"2005","journal-title":"Curr. Top. Med.\nChem."},{"key":"2026081804404452400_cit5","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1021\/ci400731w","article-title":"Fragment-based\nlead discovery and design","volume":"54","author":"Joseph-McCarthy","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/prot.340110104","article-title":"Functionality maps of binding sites: A multiple copy\nsimultaneous search method","volume":"11","author":"Miranker","year":"1991","journal-title":"Proteins: Struct.,\nFunct., Genet."},{"key":"2026081804404452400_cit7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1023\/a:1008184403558","article-title":"De novo design\nof molecular architectures by evolutionary assembly of drug-derived\nbuilding blocks","volume":"14","author":"Schneider","year":"2000","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"2026081804404452400_cit8","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.ejmech.2018.07.042","article-title":"In silico fragment-based drug design\nwith SEED","volume":"156","author":"Marchand","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"2026081804404452400_cit9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/bf00124387","article-title":"The computer\nprogram LUDI: A new method for the de novo design of enzyme inhibitors","volume":"6","author":"Bo\u0308hm","year":"1992","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"2026081804404452400_cit10","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1006\/jmbi.1996.0477","article-title":"A Fast Flexible Docking\nMethod using an Incremental Construction Algorithm","volume":"261","author":"Rarey","year":"1996","journal-title":"J. Mol. Biol."},{"key":"2026081804404452400_cit11","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1021\/ci300495r","article-title":"S4MPLE\ue5f8Sampler\nFor Multiple Protein-Ligand Entities:\nSimultaneous Docking of Several Entities","volume":"53","author":"Hoffer","year":"2013","journal-title":"J.\nChem. Inf. Model."},{"key":"2026081804404452400_cit12","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/cmdc.200500102","article-title":"FLEXNOVO: Structure-based\nsearching in large fragment spaces","volume":"1","author":"Degen","year":"2006","journal-title":"ChemMedChem"},{"key":"2026081804404452400_cit13","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1021\/ci6005307","article-title":"Flux (2): Comparison of molecular\nmutation and crossover\noperators for ligand-based de novo design","volume":"47","author":"Fechner","year":"2007","journal-title":"J.\nChem. Inf. Model."},{"key":"2026081804404452400_cit14","doi-asserted-by":"publisher","first-page":"4077","DOI":"10.1021\/acs.jcim.9b00516","article-title":"DENOPTIM: Software for Computational\nde Novo Design of Organic and Inorganic Molecules","volume":"59","author":"Foscato","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit15","doi-asserted-by":"publisher","first-page":"4171","DOI":"10.1021\/acs.jmedchem.5b00886","article-title":"OpenGrowth: An Automated and Rational\nAlgorithm for Finding New Protein Ligands","volume":"59","author":"Che\u0301ron","year":"2016","journal-title":"J.\nMed. Chem."},{"key":"2026081804404452400_cit16","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.ejmech.2018.11.075","article-title":"NAOMInext\ue5f8Synthetically feasible\nfragment growing in a structure-based design context","volume":"163","author":"Sommer","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"2026081804404452400_cit17","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1021\/acs.jcim.5b00203","article-title":"SCUBIDOO: A Large yet\nScreenable and Easily Searchable Database of\nComputationally Created Chemical Compounds Optimized toward High Likelihood\nof Synthetic Tractability","volume":"55","author":"Chevillard","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002380","article-title":"DOGS: Reaction-Driven\nde novo Design of Bioactive Compounds","volume":"8","author":"Hartenfeller","year":"2012","journal-title":"PLoS\nComput. Biol."},{"key":"2026081804404452400_cit19","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3389\/fchem.2018.00315","article-title":"Advances in the\nDevelopment of Shape Similarity Methods\nand Their Application in Drug Discovery","volume":"6","author":"Kumar","year":"2018","journal-title":"Front.\nChem."},{"key":"2026081804404452400_cit20","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1021\/ci100350u","article-title":"LigBuilder 2: A practical\nde novo drug design approach","volume":"51","author":"Yuan","year":"2011","journal-title":"J. Chem. Inf.\nModel."},{"key":"2026081804404452400_cit21","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1021\/acs.jcim.9b00198","article-title":"Discovery of Potent\nInhibitors of 11\u03b2-Hydroxysteroid Dehydrogenase\nType 1 Using a Novel Growth-Based Protocol of in Silico Screening\nand Optimization in CONTOUR","volume":"59","author":"Liu","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit22","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1021\/acs.jmedchem.6b00725","article-title":"When Does Chemical Elaboration Induce\na Ligand To Change\nIts Binding Mode?","volume":"60","author":"Malhotra","year":"2017","journal-title":"J. Med. Chem."},{"key":"2026081804404452400_cit23","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1021\/ci2003363","article-title":"SERAPhiC: A Benchmark for in Silico Fragment-Based\nDrug Design","volume":"51","author":"Favia","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit24","doi-asserted-by":"publisher","first-page":"4245","DOI":"10.1021\/acs.jmedchem.7b00101","article-title":"Large-Scale Analysis\nof Hydrogen Bond Interaction Patterns in Protein-Ligand Interfaces","volume":"60","author":"Nittinger","year":"2017","journal-title":"J. Med. Chem."},{"key":"2026081804404452400_cit25","doi-asserted-by":"publisher","first-page":"W576","DOI":"10.1093\/nar\/gkv402","article-title":"NGL Viewer: a web application for molecular visualization","volume":"43","author":"Rose","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2026081804404452400_cit26","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1021\/acs.jcim.8b00704","article-title":"Conformator: A Novel Method for the Generation of Conformer Ensembles","volume":"59","author":"Friedrich","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit27","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1021\/acs.accounts.6b00491","article-title":"Forging the Basis for\nDeveloping Protein\u2013Ligand Interaction\nScoring Functions","volume":"50","author":"Liu","year":"2017","journal-title":"Acc. Chem. Res."},{"key":"2026081804404452400_cit28","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/s1359-6446(03)02831-9","article-title":"A \u2018Rule\nof Three\u2019\nfor fragment-based lead discovery?","volume":"8","author":"Congreve","year":"2003","journal-title":"Drug Discovery\nToday"},{"key":"2026081804404452400_cit29","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1021\/acs.jcim.8b00545","article-title":"Comparative\nAssessment of Scoring Functions: The CASF-2016\nUpdate","volume":"59","author":"Su","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit30","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1517\/17460441.2014.872623","article-title":"The future of crystallography\nin drug discovery","volume":"9","author":"Zheng","year":"2014","journal-title":"Expert Opin. Drug Discovery"},{"key":"2026081804404452400_cit31","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1021\/acs.jcim.5b00588","article-title":"SIENA: Efficient Compilation\nof Selective Protein Binding Site Ensembles","volume":"56","author":"Bietz","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804404452400_cit32","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1021\/jm0603365","article-title":"Comparison\nof Shape-Matching and\nDocking as Virtual Screening Tools","volume":"50","author":"Hawkins","year":"2007","journal-title":"J. Med.\nChem."},{"key":"2026081804404452400_cit33","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1016\/j.bpj.2018.02.038","article-title":"Ensemble\nDocking in Drug Discovery","volume":"114","author":"Amaro","year":"2018","journal-title":"Biophys. J."},{"key":"2026081804404452400_cit34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1021\/acs.jcim.5b00522","article-title":"Torsion Library Reloaded:\nA New Version of Expert-Derived SMARTS Rules for Assessing Conformations\nof Small Molecules","volume":"56","author":"Guba","year":"2016","journal-title":"J. Chem. Inf. Model."}],"container-title":["Journal of Chemical Information and Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.0c00920","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/60\/12\/6269\/9624500\/ci0c00920.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/60\/12\/6269\/9624500\/ci0c00920.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:42:04Z","timestamp":1787046124000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/60\/12\/6269\/891359\/Shape-Based-Descriptors-for-Efficient-Structure"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,16]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,11,16]]},"published-print":{"date-parts":[[2020,12,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.0c00920","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,16]]}}}