{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T02:02:28Z","timestamp":1788746548029,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["ZD2017002"],"award-info":[{"award-number":["ZD2017002"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Nature Science Foundation of China","award":["31772208"],"award-info":[{"award-number":["31772208"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an iron-dependent non-heme oxygenase involved in the catabolic pathway of tyrosine, which is an important enzyme in the transformation of 4-hydroxyphenylpyruvic acid to homogentisic acid, and thus being considered as herbicide target. Within this study, a set of multiple structure-based pharmacophore models for HPPD inhibitors were developed. The ZINC and natural product database were virtually screened, and 29 compounds were obtained. The binding mode of HPPD and its inhibitors obtained through molecular docking study showed that the residues of Phe424, Phe381, His308, His226, Gln307 and Glu394 were crucial for activity. Molecular-mechanics-generalized born surface area (MM\/GBSA) results showed that the coulomb force, lipophilic and van der Waals (vdW) interactions made major contributions to the binding affinity. These efforts will greatly contribute to design novel and effective HPPD inhibitory herbicides.<\/jats:p>","DOI":"10.3390\/ijms21155546","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"5546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Based on the Virtual Screening of Multiple Pharmacophores, Docking and Molecular Dynamics Simulation Approaches toward the Discovery of Novel HPPD Inhibitors"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-6879","authenticated-orcid":false,"given":"Ying","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-4056","authenticated-orcid":false,"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structure-Based Drug Design &amp; Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7731-752X","authenticated-orcid":false,"given":"Fei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.scitotenv.2016.06.064","article-title":"Herbicide-related signaling in plants reveals novel insights for herbicide use strategies, environmental risk assessment and global change assessment challenges","volume":"569","author":"Alberto","year":"2016","journal-title":"Sci. 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