guest ::
| Home > Publications database > Predictions of the Poses and Affinity of a Ligand over the Entire Surface of a NEET Protein: The Case of Human MitoNEET > print |
| Home > Publications database > Predictions of the Poses and Affinity of a Ligand over the Entire Surface of a NEET Protein: The Case of Human MitoNEET > print |
| 001 | 943415 | ||
| 005 | 20251009202052.0 | ||
| 024 | 7 | _ | |a 10.1021/acs.jcim.2c01280 |2 doi |
| 024 | 7 | _ | |a 0095-2338 |2 ISSN |
| 024 | 7 | _ | |a 1549-9596 |2 ISSN |
| 024 | 7 | _ | |a 1520-5142 |2 ISSN |
| 024 | 7 | _ | |a (BIS |2 ISSN |
| 024 | 7 | _ | |a 44.2004) |2 ISSN |
| 024 | 7 | _ | |a 1549-960X |2 ISSN |
| 024 | 7 | _ | |a 2128/33832 |2 Handle |
| 024 | 7 | _ | |a 36623826 |2 pmid |
| 024 | 7 | _ | |a WOS:000914450700001 |2 WOS |
| 024 | 7 | _ | |a 10.34734/FZJ-2023-01001 |2 datacite_doi |
| 037 | _ | _ | |a FZJ-2023-01001 |
| 082 | _ | _ | |a 540 |
| 100 | 1 | _ | |a Zuo, Ke |0 P:(DE-Juel1)192214 |b 0 |u fzj |
| 245 | _ | _ | |a Predictions of the Poses and Affinity of a Ligand over the Entire Surface of a NEET Protein: The Case of Human MitoNEET |
| 260 | _ | _ | |a Washington, DC |c 2023 |b American Chemical Society |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1676959059_12538 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Human NEET proteins contain two [2Fe–2S] iron–sulfur clusters, bound to three Cys residues and one His residue. They exist in two redox states. Recently, these proteins have revealed themselves as attractive drug targets for mitochondrial dysfunction-related diseases, such as type 2 diabetes, Wolfram syndrome 2, and cancers. Unfortunately, the lack of information and mechanistic understanding of ligands binding to the whole functional, cytoplasmatic domain has limited rational drug design approaches. Here, we use an enhanced sampling technique, volume-based metadynamics, recently developed by a team involving some of us, to predict the poses and affinity of the 2-benzamido-4-(1,2,3,4-tetrahydronaphthalen-2-yl)-thiophene-3-carboxylate ligand to the entire surface of the cytoplasmatic domain of the human NEET protein mitoNEET (mNT) in an aqueous solution. The calculations, based on the recently published X-ray structure of the complex, are consistent with the measured affinity. The calculated free energy landscape revealed that the ligand can bind in multiple sites and with poses other than the one found in the X-ray. This difference is likely to be caused by crystal packing effects that allow the ligand to interact with multiple adjacent NEET protein copies. Such extra contacts are of course absent in the solution; therefore, the X-ray pose is only transient in our calculations, where the binding free energy correlates with the number of contacts. We further evaluated how the reduction and protonation of the Fe-bound histidine, as well as temperature, can affect ligand binding. Both such modifications introduce the possibility for the ligand to bind in an area of the protein other than the one observed in the X-ray, with no or little impact on affinity. Overall, our study can provide insights on the molecular recognition mechanisms of ligand binding to mNT in different oxidative conditions, possibly helping rational drug design of NEET ligands. |
| 536 | _ | _ | |a 5241 - Molecular Information Processing in Cellular Systems (POF4-524) |0 G:(DE-HGF)POF4-5241 |c POF4-524 |f POF IV |x 0 |
| 536 | _ | _ | |a 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) |0 G:(DE-HGF)POF4-5111 |c POF4-511 |f POF IV |x 1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: juser.fz-juelich.de |
| 700 | 1 | _ | |a Capelli, Riccardo |0 P:(DE-Juel1)174546 |b 1 |
| 700 | 1 | _ | |a Rossetti, Giulia |0 P:(DE-Juel1)145921 |b 2 |
| 700 | 1 | _ | |a Nechushtai, Rachel |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Carloni, Paolo |0 P:(DE-Juel1)145614 |b 4 |e Corresponding author |
| 773 | _ | _ | |a 10.1021/acs.jcim.2c01280 |g Vol. 63, no. 2, p. 643 - 654 |0 PERI:(DE-600)1491237-5 |n 2 |p 643 - 654 |t Journal of chemical information and modeling |v 63 |y 2023 |x 0095-2338 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/943415/files/Invoice_APC600376339.pdf |
| 856 | 4 | _ | |y Published on 2023-01-09. Available in OpenAccess from 2024-01-09. |u https://juser.fz-juelich.de/record/943415/files/Authors%27%20version.docx |
| 856 | 4 | _ | |y OpenAccess |u https://juser.fz-juelich.de/record/943415/files/acs.jcim.2c01280-1-1.pdf |
| 909 | C | O | |o oai:juser.fz-juelich.de:943415 |p openaire |p open_access |p OpenAPC |p driver |p VDB |p openCost |p dnbdelivery |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 0 |6 P:(DE-Juel1)192214 |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 2 |6 P:(DE-Juel1)145921 |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 4 |6 P:(DE-Juel1)145614 |
| 913 | 1 | _ | |a DE-HGF |b Key Technologies |l Natural, Artificial and Cognitive Information Processing |1 G:(DE-HGF)POF4-520 |0 G:(DE-HGF)POF4-524 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-500 |4 G:(DE-HGF)POF |v Molecular and Cellular Information Processing |9 G:(DE-HGF)POF4-5241 |x 0 |
| 913 | 1 | _ | |a DE-HGF |b Key Technologies |l Engineering Digital Futures – Supercomputing, Data Management and Information Security for Knowledge and Action |1 G:(DE-HGF)POF4-510 |0 G:(DE-HGF)POF4-511 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-500 |4 G:(DE-HGF)POF |v Enabling Computational- & Data-Intensive Science and Engineering |9 G:(DE-HGF)POF4-5111 |x 1 |
| 914 | 1 | _ | |y 2023 |
| 915 | p | c | |a APC keys set |0 PC:(DE-HGF)0000 |2 APC |
| 915 | p | c | |a Local Funding |0 PC:(DE-HGF)0001 |2 APC |
| 915 | p | c | |a DFG OA Publikationskosten |0 PC:(DE-HGF)0002 |2 APC |
| 915 | p | c | |a Helmholtz: American Chemical Society 01/01/2023 |0 PC:(DE-HGF)0122 |2 APC |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2023-10-21 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2023-10-21 |
| 915 | _ | _ | |a Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 |0 LIC:(DE-HGF)CCBYNCND4 |2 HGFVOC |
| 915 | _ | _ | |a Embargoed OpenAccess |0 StatID:(DE-HGF)0530 |2 StatID |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b J CHEM INF MODEL : 2022 |d 2023-10-21 |
| 915 | _ | _ | |a IF >= 5 |0 StatID:(DE-HGF)9905 |2 StatID |b J CHEM INF MODEL : 2022 |d 2023-10-21 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2022-11-16 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2023-10-21 |
| 915 | _ | _ | |a OpenAccess |0 StatID:(DE-HGF)0510 |2 StatID |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1150 |2 StatID |b Current Contents - Physical, Chemical and Earth Sciences |d 2023-10-21 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2022-11-16 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2023-10-21 |
| 920 | _ | _ | |l yes |
| 920 | 1 | _ | |0 I:(DE-Juel1)IAS-5-20120330 |k IAS-5 |l Computational Biomedicine |x 0 |
| 920 | 1 | _ | |0 I:(DE-Juel1)INM-9-20140121 |k INM-9 |l Computational Biomedicine |x 1 |
| 920 | 1 | _ | |0 I:(DE-Juel1)JSC-20090406 |k JSC |l Jülich Supercomputing Center |x 2 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a UNRESTRICTED |
| 980 | _ | _ | |a I:(DE-Juel1)IAS-5-20120330 |
| 980 | _ | _ | |a I:(DE-Juel1)INM-9-20140121 |
| 980 | _ | _ | |a I:(DE-Juel1)JSC-20090406 |
| 980 | _ | _ | |a APC |
| 980 | 1 | _ | |a APC |
| 980 | 1 | _ | |a FullTexts |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|