{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:31:14Z","timestamp":1785490274712,"version":"3.56.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":371,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Structure"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.str.2021.09.004","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T18:17:21Z","timestamp":1633457841000},"page":"181-189.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["MANORAA: A machine learning platform to guide protein-ligand design by anchors and influential distances"],"prefix":"10.1016","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-3303","authenticated-orcid":false,"given":"Duangrudee","family":"Tanramluk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-8283","authenticated-orcid":false,"given":"Danaya","family":"Pakotiprapha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-3427","authenticated-orcid":false,"given":"Sakao","family":"Phoochaijaroen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattra","family":"Chantravisut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-7652","authenticated-orcid":false,"given":"Sirikanya","family":"Thampradid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-1467","authenticated-orcid":false,"given":"Jarunee","family":"Vanichtanankul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalita","family":"Narupiyakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2657-3387","authenticated-orcid":false,"given":"Ruj","family":"Akavipat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6800-8944","authenticated-orcid":false,"given":"Jirundon","family":"Yuvaniyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.str.2021.09.004_bib1","doi-asserted-by":"crossref","first-page":"18477","DOI":"10.1073\/pnas.2000585117","article-title":"Machine learning classification can reduce false positives in structure-based virtual screening","volume":"117","author":"Adeshina","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.str.2021.09.004_bib2","doi-asserted-by":"crossref","first-page":"D674","DOI":"10.1093\/nar\/gkm911","article-title":"Binding MOAD, a high-quality protein\u2013ligand database","volume":"36","author":"Benson","year":"2008","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib3","doi-asserted-by":"crossref","first-page":"D1056","DOI":"10.1093\/nar\/gky1133","article-title":"Open Targets Platform: new developments and updates two years on","volume":"47","author":"Carvalho-Silva","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib4","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1107\/S0907444904001544","article-title":"Characterization, crystallization and preliminary X-ray analysis of bifunctional dihydrofolate reductase-thymidylate synthase from Plasmodium falciparum","volume":"60","author":"Chitnumsub","year":"2004","journal-title":"Acta Crystallographica. Sect.\u00a0D, Biol. Crystallogr."},{"key":"10.1016\/j.str.2021.09.004_bib5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.chemolab.2004.12.011","article-title":"Performance of some variable selection methods when multicollinearity is present","volume":"78","author":"Chong","year":"2005","journal-title":"Chemometrics Intell. Lab. Syst."},{"key":"10.1016\/j.str.2021.09.004_bib6","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.drudis.2020.03.003","article-title":"Machine learning models for drug\u2013target interactions: current knowledge and future directions","volume":"25","author":"D\u2019Souza","year":"2020","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.str.2021.09.004_bib7","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1128\/AAC.37.7.1400","article-title":"Characterization of the gene for\u00a0chromosomal trimethoprim-sensitive dihydrofolate reductase of Staphylococcus aureus ATCC 25923","volume":"37","author":"Dale","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.str.2021.09.004_bib8","doi-asserted-by":"crossref","first-page":"W612","DOI":"10.1093\/nar\/gkv352","article-title":"ChEMBL web services: streamlining access to drug discovery data and utilities","volume":"43","author":"Davies","year":"2015","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib9","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1021\/acs.jpclett.1c00189","article-title":"DeepBAR: a fast and exact method for binding free energy computation","volume":"12","author":"Ding","year":"2021","journal-title":"J.\u00a0Phys. Chem. Lett."},{"key":"10.1016\/j.str.2021.09.004_bib10","doi-asserted-by":"crossref","first-page":"e1006483","DOI":"10.1371\/journal.pcbi.1006483","article-title":"A benchmark driven guide to binding site comparison: an exhaustive evaluation using tailor-made data sets (ProSPECCTs)","volume":"14","author":"Ehrt","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.str.2021.09.004_bib11","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot. Acta crystallographica","volume":"66","author":"Emsley","year":"2010","journal-title":"Sect. D Biol. Crystallogr."},{"key":"10.1016\/j.str.2021.09.004_bib12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nchembio.296","article-title":"The art of the chemical probe","volume":"6","author":"Frye","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.str.2021.09.004_bib13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12265-011-9259-1","article-title":"Meet me halfway: when genomics meets structural bioinformatics","volume":"4","author":"Gong","year":"2011","journal-title":"J.\u00a0Cardiovasc. Trans. Res."},{"key":"10.1016\/j.str.2021.09.004_bib14","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/0003-2697(67)90179-0","article-title":"Effect of substrate decomposition on the spectrophotometric assay of dihydrofolate reductase","volume":"21","author":"Hillcoat","year":"1967","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.str.2021.09.004_bib15","doi-asserted-by":"crossref","first-page":"126641","DOI":"10.1016\/j.bmcl.2019.126641","article-title":"Structure-based rational design of staurosporine-based fluorescent probe with broad-ranging kinase affinity for kinase panel application","volume":"29","author":"Hirozane","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.str.2021.09.004_bib16","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1021\/acs.jcim.8b00478","article-title":"Machine learning in drug discovery","volume":"58","author":"Hochreiter","year":"2018","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.str.2021.09.004_bib17","doi-asserted-by":"crossref","first-page":"D884","DOI":"10.1093\/nar\/gkaa942","article-title":"Ensembl 2021","volume":"49","author":"Howe","year":"2021","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.str.2021.09.004_bib19","doi-asserted-by":"crossref","first-page":"112263","DOI":"10.1016\/j.ejmech.2020.112263","article-title":"Flexible diaminodihydrotriazine inhibitors of Plasmodium falciparum dihydrofolate reductase: binding strengths, modes of binding and their antimalarial activities","volume":"195","author":"Kamchonwongpaisan","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.str.2021.09.004_bib20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-1-4939-8639-2_2","article-title":"Finding potential multitarget ligands using PubChem","volume":"1825","author":"Kim","year":"2018","journal-title":"Methods Mol. Biol. (Clifton, N.J.)"},{"key":"10.1016\/j.str.2021.09.004_bib22","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1016\/j.drudis.2019.07.006","article-title":"Deep learning in drug discovery: opportunities, challenges and future prospects","volume":"24","author":"Lavecchia","year":"2019","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.str.2021.09.004_bib23","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0021-9258(18)89744-7","article-title":"Dihydrofolate reductase. The stereochemistry of inhibitor selectivity","volume":"260","author":"Matthews","year":"1985","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.str.2021.09.004_bib24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1107\/S0907444911001314","article-title":"REFMAC5 for the refinement of macromolecular crystal structures","volume":"67","author":"Murshudov","year":"2011","journal-title":"Acta Crystallographica. Section D, Biol. Crystallogr."},{"key":"10.1016\/j.str.2021.09.004_bib25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10822-018-0146-6","article-title":"Mathematical deep learning for pose and binding affinity prediction and ranking in D3R Grand Challenges","volume":"33","author":"Nguyen","year":"2019","journal-title":"J.\u00a0Comput. Aided Mol. Des."},{"key":"10.1016\/j.str.2021.09.004_bib26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.str.2021.09.004_bib27","doi-asserted-by":"crossref","first-page":"15908","DOI":"10.1016\/S0021-9258(18)47675-2","article-title":"Kinetic analysis of the mechanism of Escherichia coli dihydrofolate reductase","volume":"262","author":"Penner","year":"1987","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.str.2021.09.004_bib28","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1107\/S090744499900935X","article-title":"The finer things in X-ray diffraction data collection","volume":"55","author":"Pflugrath","year":"1999","journal-title":"Acta\u00a0Crystallogr. Sect. D"},{"key":"10.1016\/j.str.2021.09.004_bib29","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1093\/bioinformatics\/bty419","article-title":"NGL viewer: web-based molecular graphics for large complexes","volume":"34","author":"Rose","year":"2018","journal-title":"Bioinformatics"},{"key":"10.1016\/j.str.2021.09.004_bib30","first-page":"bat049","article-title":"CREDO: A Structural Interactomics Database for Drug Discovery","volume":"2013","author":"Schreyer","year":"2013","journal-title":"Database J. Biol. Databases Curation"},{"key":"10.1016\/j.str.2021.09.004_bib31","series-title":"Analysis of amino acid environments in proteins by statistical approaches. Master of Science in Bioinformatics","author":"Tanramluk","year":"2005"},{"key":"10.1016\/j.str.2021.09.004_bib32","doi-asserted-by":"crossref","first-page":"W514","DOI":"10.1093\/nar\/gkw314","article-title":"MANORAA (Mapping Analogous Nuclei onto Residue and Affinity) for identifying protein\u2013ligand fragment interaction, pathways and SNPs","volume":"44","author":"Tanramluk","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1747-0285.2009.00832.x","article-title":"On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine","volume":"74","author":"Tanramluk","year":"2009","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.str.2021.09.004_bib34","series-title":"Kinetic Studies of Wild-type and Mutant Staphylococcus aureus Dihydrofolate Reductase (SaDHFR) for Drug Discovery. Master of Science Program in Biochemistry","author":"Thampradid","year":"2016"},{"key":"10.1016\/j.str.2021.09.004_bib36","first-page":"D480","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","year":"2020","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib37","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-021-03828-1","article-title":"Highly accurate protein structure prediction for the human proteome","author":"Tunyasuvunakool","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.str.2021.09.004_bib38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1107\/S0907444909042589","article-title":"Molecular replacement with MOLREP","volume":"66","author":"Vagin","year":"2010","journal-title":"Acta Crystallogr. Sect. D"},{"key":"10.1016\/j.str.2021.09.004_bib39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1107\/S0907444998006684","article-title":"SFCHECK: a unified set of procedures for evaluating the quality of macromolecular structure-factor data and their agreement with the atomic model","volume":"55","author":"Vaguine","year":"1999","journal-title":"Acta Crystallogr. Sect. D"},{"key":"10.1016\/j.str.2021.09.004_bib40","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1021\/cb200124r","article-title":"Trypanosomal dihydrofolate reductase reveals natural antifolate resistance","volume":"6","author":"Vanichtanankul","year":"2011","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.str.2021.09.004_bib41","doi-asserted-by":"crossref","first-page":"D385","DOI":"10.1093\/nar\/gkv1047","article-title":"PDBe: improved accessibility of macromolecular structure data from PDB and EMDB","volume":"44","author":"Velankar","year":"2016","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.str.2021.09.004_bib42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S0907444910045749","article-title":"Overview of the CCP4 suite and current developments","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Crystallogr. Sect. D"},{"key":"10.1016\/j.str.2021.09.004_bib43","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.chembiol.2010.05.013","article-title":"Probing the probes: fitness factors for small molecule tools","volume":"17","author":"Workman","year":"2010","journal-title":"Chem. Biol."},{"key":"10.1016\/j.str.2021.09.004_bib44","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nsb921","article-title":"Insights into antifolate resistance from malarial DHFR-TS structures","volume":"10","author":"Yuvaniyama","year":"2003","journal-title":"Nat. Struct. Biol."}],"container-title":["Structure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969212621003324?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969212621003324?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T02:41:30Z","timestamp":1760841690000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969212621003324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["S0969212621003324"],"URL":"https:\/\/doi.org\/10.1016\/j.str.2021.09.004","relation":{"is-basis-for":[{"id-type":"doi","id":"10.52843\/cassyni.vlsgln","asserted-by":"object"}]},"ISSN":["0969-2126"],"issn-type":[{"value":"0969-2126","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"MANORAA: A machine learning platform to guide protein-ligand design by anchors and influential distances","name":"articletitle","label":"Article Title"},{"value":"Structure","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.str.2021.09.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}