Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김철근 | - |
dc.date.accessioned | 2022-03-22T00:43:39Z | - |
dc.date.available | 2022-03-22T00:43:39Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.citation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, no. 15, article no. 5248 | en_US |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | https://www.mdpi.com/1422-0067/21/15/5248 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/169277 | - |
dc.description.abstract | Intrinsically disordered proteins exist as highly dynamic conformational ensembles of diverse forms. However, the majority of virtual screening only focuses on proteins with defined structures. This means that computer-aided drug discovery is restricted. As a breakthrough, understanding the structural characteristics of intrinsically disordered proteins and its application can open the gate for unrestricted drug discovery. First, we segmented the target disorder-to-order transition region into a series of overlapping 20-amino-acid-long peptides. Folding prediction generated diverse conformations of these peptides. Next, we applied molecular docking, new evaluation score function, and statistical analysis. This approach successfully distinguished known compounds and their corresponding binding regions. Especially, Myc proto-oncogene protein (MYC) inhibitor 10058F4 was well distinguished from others of the chemical compound library. We also studied differences between the two Methyl-CpG-binding domain protein 2 (MBD2) inhibitors (ABA (2-amino-N-[[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-acetamide) and APC ((R)-(3-(2-Amino-acetylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester))). Both compounds bind MBD2 through electrostatic interaction behind its p66α-binding site. ABA is also able to bind p66α through electrostatic interaction behind its MBD2-binding site while APC-p66α binding was nonspecific. Therefore, structural heterogeneity mimicking of the disorder-to-order transition region at the peptide level and utilization of the new docking score function represent a useful approach that can efficiently discriminate compounds for expanded virtual screening toward intrinsically disordered proteins. | en_US |
dc.description.sponsorship | This work was supported by the Basic Science Research Program (NRF-2020R1A2C2009112 to C.G.K.) and the Bio& Medical Technology Development program (NRF-2017M3A9C8027975 and NRF-2020M3A9G4021041 to C.G.K.), National Research Foundation (NRF), Republic of Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.subject | disorder-to-order transition | en_US |
dc.subject | computer-aided drug discovery | en_US |
dc.subject | protein–protein interaction inhibitor | en_US |
dc.subject | conformational diversity mimicking | en_US |
dc.subject | peptide docking | en_US |
dc.title | Drug discovery targeting the disorder-to-order transition regions through the conformational diversity mimicking and statistical analysis | en_US |
dc.type | Article | en_US |
dc.relation.no | 15 | - |
dc.relation.volume | 21 | - |
dc.identifier.doi | 10.3390/ijms21155248 | - |
dc.relation.page | 1-16 | - |
dc.relation.journal | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.contributor.googleauthor | Na, Insung | - |
dc.contributor.googleauthor | Choi, Sungwoo | - |
dc.contributor.googleauthor | Son, Seung Han | - |
dc.contributor.googleauthor | Uversky, Vladimir N. | - |
dc.contributor.googleauthor | Kim, Chul Geun | - |
dc.relation.code | 2020050347 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF NATURAL SCIENCES[S] | - |
dc.sector.department | DEPARTMENT OF LIFE SCIENCE | - |
dc.identifier.pid | cgkim | - |
dc.identifier.orcid | https://orcid.org/0000-0002-5848-3338 | - |
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