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The last two decades witnessed intensive efforts to discover 20S proteasome inhibitors with significant chemical diversity and efficacy. To date, the US FDA approved to market three proteasome inhibitors: bortezomib, carfilzomib, and ixazomib. However new, safer and more efficient drugs are still required. Computer-aided drug discovery has long being used in drug discovery campaigns targeting the human proteasome. The aim of this review is to illustrate selected in silico methods like homology modeling, molecular docking, pharmacophore modeling, virtual screening, and combined methods that have been used in proteasome inhibitors discovery. Applications of these methods to proteasome inhibitors discovery will also be presented and discussed to raise improvements in this particular field.<\/jats:p>","DOI":"10.3390\/molecules21070927","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T09:38:03Z","timestamp":1468834683000},"page":"927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Computational Approaches for the Discovery of Human Proteasome Inhibitors: An Overview"],"prefix":"10.3390","volume":"21","author":[{"given":"Romina","family":"Guedes","sequence":"first","affiliation":[{"name":"iMed.ULisboa, Research Institute for Medicines, Faculdade de Farm\u00e1cia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-9452","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Serra","sequence":"additional","affiliation":[{"name":"iMed.ULisboa, Research Institute for Medicines, Faculdade de Farm\u00e1cia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Jorge","family":"Salvador","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Farmac\u00eautica, Faculdade de Farm\u00e1cia da Universidade de Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade-Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"Center for Neurosciences and Cell Biology, Universidade de Coimbra, Rua Larga-Faculdade de Medicina, P\u00f3lo I, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-9181","authenticated-orcid":false,"given":"Rita","family":"Guedes","sequence":"additional","affiliation":[{"name":"iMed.ULisboa, Research Institute for Medicines, Faculdade de Farm\u00e1cia da Universidade de Lisboa, Av. 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