Atomic Simulation of the Binding of JAK1 and JAK2 with the Selective Inhibitor Ruxolitinib
Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular manifestations. Cytokines regulate a wide range of inflammatory processes involved in the pathogenesis of rheumatoid arthritis and contribut...
Saved in:
| Published in: | International journal of molecular sciences Vol. 23; no. 18; p. 10466 |
|---|---|
| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Basel
MDPI AG
09-09-2022
MDPI |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular manifestations. Cytokines regulate a wide range of inflammatory processes involved in the pathogenesis of rheumatoid arthritis and contribute to the induction of autoimmunity and chronic inflammation. Janus-associated kinase (JAK) and signal transducer and activator of transcription (STAT) proteins mediate cell signaling from cytokine receptors, and are involved in the pathogenesis of autoimmune and inflammatory diseases. Targeted small-molecule drugs that inhibit the functional activity of JAK proteins are used in clinical practice for the treatment of rheumatoid arthritis. In our study, we modeled the interactions of the small-molecule drug ruxolitinib with JAK1 and JAK2 isoforms and determined the binding selectivity using molecular docking. Molecular modeling data show that ruxolitinib selectively binds the JAK1 and JAK2 isoforms with a binding affinity of −8.3 and −8.0 kcal/mol, respectively. The stabilization of ligands in the cavity of kinases occurs primarily through hydrophobic interactions. The amino acid residues of the protein globules of kinases that are responsible for the correct positioning of the drug ruxolitinib and its retention have been determined. |
|---|---|
| AbstractList | Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular manifestations. Cytokines regulate a wide range of inflammatory processes involved in the pathogenesis of rheumatoid arthritis and contribute to the induction of autoimmunity and chronic inflammation. Janus-associated kinase (JAK) and signal transducer and activator of transcription (STAT) proteins mediate cell signaling from cytokine receptors, and are involved in the pathogenesis of autoimmune and inflammatory diseases. Targeted small-molecule drugs that inhibit the functional activity of JAK proteins are used in clinical practice for the treatment of rheumatoid arthritis. In our study, we modeled the interactions of the small-molecule drug ruxolitinib with JAK1 and JAK2 isoforms and determined the binding selectivity using molecular docking. Molecular modeling data show that ruxolitinib selectively binds the JAK1 and JAK2 isoforms with a binding affinity of −8.3 and −8.0 kcal/mol, respectively. The stabilization of ligands in the cavity of kinases occurs primarily through hydrophobic interactions. The amino acid residues of the protein globules of kinases that are responsible for the correct positioning of the drug ruxolitinib and its retention have been determined. |
| Author | Kopylov, Arthur T Kondratyev, Maxim Nikolsky, Kirill S Stepanov, Alexander A Rudnev, Vladimir R Malsagova, Kristina A Kulikova, Liudmila I Kaysheva, Anna L Petrovsky, Denis V |
| AuthorAffiliation | 2 Biobanking Group, Branch of Institute of Biomedical Chemistry “Scientific and Education Center”, 109028 Moscow, Russia 3 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia 1 Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia 4 Institute of Mathematical Problems of Biology RAS—The Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, 142290 Pushchino, Russia |
| AuthorAffiliation_xml | – name: 2 Biobanking Group, Branch of Institute of Biomedical Chemistry “Scientific and Education Center”, 109028 Moscow, Russia – name: 4 Institute of Mathematical Problems of Biology RAS—The Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, 142290 Pushchino, Russia – name: 3 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia – name: 1 Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia |
| Author_xml | – sequence: 1 givenname: Maxim orcidid: 0000-0001-6717-4206 surname: Kondratyev fullname: Kondratyev, Maxim – sequence: 2 givenname: Vladimir R. surname: Rudnev fullname: Rudnev, Vladimir R. – sequence: 3 givenname: Kirill S. surname: Nikolsky fullname: Nikolsky, Kirill S. – sequence: 4 givenname: Alexander A. orcidid: 0000-0002-9113-9440 surname: Stepanov fullname: Stepanov, Alexander A. – sequence: 5 givenname: Denis V. surname: Petrovsky fullname: Petrovsky, Denis V. – sequence: 6 givenname: Liudmila I. surname: Kulikova fullname: Kulikova, Liudmila I. – sequence: 7 givenname: Arthur T. orcidid: 0000-0002-7199-372X surname: Kopylov fullname: Kopylov, Arthur T. – sequence: 8 givenname: Kristina A. orcidid: 0000-0001-9404-1660 surname: Malsagova fullname: Malsagova, Kristina A. – sequence: 9 givenname: Anna L. orcidid: 0000-0003-4472-2016 surname: Kaysheva fullname: Kaysheva, Anna L. |
| BookMark | eNpdkktv1DAQgC3Uij7gyD0SFy4Bv-LHBWmpCiythEThwsVy_Nj1KrGL4xT49zjdqupymvHMp29G1pyBo5iiA-AVgm8JkfBd2I0TJkggSBl7Bk4RxbiFkPGjJ_kJOJumHYSY4E4-ByeE1Rbh3Sn4uSppDKa5CeM86BJSbJJvytY1H0K0IW6W55fVFWp0tEuCm9-hbO-JGzc4U8Kda9ZxG_pQUm6-zX_SEEqIoX8Bjr0eJvfyIZ6DHx8vv198bq-_flpfrK5bQztRWumRxsIizXsOYU8cFg5L1yNPpaGaW9wzSjsmTI1WeCOJ7gyE3NWys5Scg_Xea5PeqdscRp3_qqSDui-kvFE6l2AGpzzFhnAmPKScSmK09ZZ5ynppBEcSVdf7vet27kdnjYsl6-FAetiJYas26U7JrioJq4I3D4Kcfs1uKmoMk3HDoKNL86QwR3U-lZhX9PV_6C7NOdavWijWdYLBZaN2T5mcpik7_7gMgmq5AHVwAeQfVVCjNw |
| CitedBy_id | crossref_primary_10_1016_j_pharmthera_2023_108579 |
| Cites_doi | 10.1529/biophysj.107.116095 10.1088/0953-8984/21/37/373102 10.1007/s00249-011-0700-9 10.3390/ijms22115931 10.1021/bi961149j 10.1063/1.448118 10.1186/1472-6882-5-22 10.1016/j.softx.2015.06.001 10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M 10.1021/bi00199a029 10.1021/bi00260a009 10.1093/nar/gkh429 10.1134/S000629791010007X 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H 10.1136/ard.2003.015826 10.1146/annurev.biophys.36.040306.132608 10.1016/0014-5793(91)80706-9 10.1093/rheumatology/40.10.1175 10.1016/j.smhs.2021.02.005 10.1016/0014-5793(84)80039-3 10.1038/nsb0694-388 10.1016/0014-5793(92)80072-O 10.1093/nar/gkz456 10.1186/s13075-018-1624-x 10.1089/107555302753507195 10.1098/rsif.2015.0876 10.1007/s00421-015-3186-9 10.1007/s100670050125 10.1038/nature02261 10.1016/0140-6736(91)91770-U 10.3389/fnut.2017.00052 10.1063/1.2408420 10.4236/jbpc.2011.23033 10.1063/1.470117 |
| ContentType | Journal Article |
| Copyright | 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2022 by the authors. 2022 |
| Copyright_xml | – notice: 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2022 by the authors. 2022 |
| DBID | AAYXX CITATION 3V. 7X7 7XB 88E 8FI 8FJ 8FK 8G5 ABUWG AFKRA AZQEC BENPR CCPQU DWQXO FYUFA GHDGH GNUQQ GUQSH K9. M0S M1P M2O MBDVC PIMPY PQEST PQQKQ PQUKI PRINS Q9U 7X8 5PM DOA |
| DOI | 10.3390/ijms231810466 |
| DatabaseName | CrossRef ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) Research Library (Alumni Edition) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials ProQuest Central ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student Research Library Prep ProQuest Health & Medical Complete (Alumni) Health & Medical Collection (Alumni Edition) Medical Database Research Library Research Library (Corporate) Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef Publicly Available Content Database Research Library Prep ProQuest Central Student ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College Research Library (Alumni Edition) ProQuest Central China ProQuest Central Health Research Premium Collection Health and Medicine Complete (Alumni Edition) ProQuest Central Korea ProQuest Research Library ProQuest Medical Library (Alumni) ProQuest Central Basic ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | Publicly Available Content Database CrossRef |
| Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: http://www.doaj.org/ sourceTypes: Open Website |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1422-0067 |
| ExternalDocumentID | oai_doaj_org_article_f42c3768f047493cadfd6f46b9c87191 10_3390_ijms231810466 |
| GrantInformation_xml | – fundername: Russian Science Foundation grantid: 21-14-00381 |
| GroupedDBID | --- 29J 2WC 3V. 53G 5GY 5VS 7X7 88E 8FE 8FG 8FH 8FI 8FJ 8G5 A8Z AADQD AAFWJ AAHBH AAYXX ABDBF ABJCF ABUWG ACGFO ACIHN ACIWK ACPRK ADBBV AEAQA AENEX AFKRA AFPKN AFZYC ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BBNVY BCNDV BENPR BHPHI BPHCQ BVXVI CCPQU CITATION CS3 D1I DIK DU5 DWQXO E3Z EBD EBS EJD ESTFP ESX F5P FRP FYUFA GNUQQ GROUPED_DOAJ GUQSH GX1 HCIFZ HH5 HMCUK HYE IAO ITC KB. KQ8 LK8 M1P M2O M48 M7P MODMG M~E O5R O5S OK1 P2P PDBOC PIMPY PQQKQ PROAC PSQYO RIG RNS RPM TR2 TUS UKHRP ~8M 7XB 8FK K9. MBDVC PQEST PQUKI PRINS Q9U 7X8 5PM |
| ID | FETCH-LOGICAL-c458t-9f1a28d1a7b700b3e28e29eb1f49c4a7d2b644568cb64d8fc93a5c007e644ed43 |
| IEDL.DBID | RPM |
| ISSN | 1422-0067 1661-6596 |
| IngestDate | Tue Oct 22 14:53:17 EDT 2024 Tue Sep 17 21:35:57 EDT 2024 Fri Oct 25 05:12:59 EDT 2024 Wed Oct 30 02:56:08 EDT 2024 Wed Aug 07 14:08:35 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 18 |
| Language | English |
| License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c458t-9f1a28d1a7b700b3e28e29eb1f49c4a7d2b644568cb64d8fc93a5c007e644ed43 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0003-4472-2016 0000-0001-9404-1660 0000-0001-6717-4206 0000-0002-7199-372X 0000-0002-9113-9440 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504736/ |
| PMID | 36142375 |
| PQID | 2716558601 |
| PQPubID | 2032341 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_f42c3768f047493cadfd6f46b9c87191 pubmedcentral_primary_oai_pubmedcentral_nih_gov_9504736 proquest_miscellaneous_2717684927 proquest_journals_2716558601 crossref_primary_10_3390_ijms231810466 |
| PublicationCentury | 2000 |
| PublicationDate | 20220909 |
| PublicationDateYYYYMMDD | 2022-09-09 |
| PublicationDate_xml | – month: 9 year: 2022 text: 20220909 day: 9 |
| PublicationDecade | 2020 |
| PublicationPlace | Basel |
| PublicationPlace_xml | – name: Basel |
| PublicationTitle | International journal of molecular sciences |
| PublicationYear | 2022 |
| Publisher | MDPI AG MDPI |
| Publisher_xml | – name: MDPI AG – name: MDPI |
| References | Fraser (ref_7) 1999; 18 Nandel (ref_29) 2011; 2 Boshkova (ref_21) 2010; 75 Drew (ref_23) 2019; 47 Efimov (ref_18) 1984; 166 Haugen (ref_8) 1991; 338 Heinig (ref_24) 2004; 32 Sandstad (ref_4) 2015; 115 Berendsen (ref_31) 1984; 81 Efimov (ref_19) 1991; 284 Malorgio (ref_3) 2021; 3 Ringertz (ref_10) 2001; 40 Kmiecik (ref_15) 2008; 94 Abraham (ref_27) 2015; 1–2 Dobson (ref_13) 2003; 426 Efimov (ref_17) 1992; 298 ref_25 Miles (ref_26) 1994; 1 Bussi (ref_30) 2007; 126 Bartlett (ref_6) 2018; 20 Chothia (ref_20) 1982; 21 Daura (ref_34) 1999; 38 McDougall (ref_11) 2002; 8 Essmann (ref_33) 1995; 103 (ref_16) 2007; 36 Abkevich (ref_12) 1994; 33 Khanna (ref_2) 2017; 4 ref_9 (ref_14) 2009; 21 Schmid (ref_28) 2011; 40 Hess (ref_32) 1997; 18 Munneke (ref_5) 2004; 63 (ref_1) 2015; 12 Berndt (ref_22) 1996; 35 |
| References_xml | – volume: 94 start-page: 726 year: 2008 ident: ref_15 article-title: Folding Pathway of the B1 Domain of Protein G Explored by Multiscale Modeling publication-title: Biophys. J. doi: 10.1529/biophysj.107.116095 contributor: fullname: Kmiecik – volume: 21 start-page: 373102 year: 2009 ident: ref_14 article-title: The Nucleation Mechanism of Protein Folding: A Survey of Computer Simulation Studies publication-title: J. Phys. Condens. Matter doi: 10.1088/0953-8984/21/37/373102 – volume: 40 start-page: 843 year: 2011 ident: ref_28 article-title: Definition and Testing of the GROMOS Force-Field Versions 54A7 and 54B7 publication-title: Eur. Biophys. J. doi: 10.1007/s00249-011-0700-9 contributor: fullname: Schmid – ident: ref_25 doi: 10.3390/ijms22115931 – volume: 35 start-page: 12723 year: 1996 ident: ref_22 article-title: Solution Structure of a Naturally-Occurring Zinc-Peptide Complex Demonstrates That the N-Terminal Zinc-Binding Module of the Lasp-1 LIM Domain Is an Independent Folding Unit publication-title: Biochemistry doi: 10.1021/bi961149j contributor: fullname: Berndt – volume: 81 start-page: 3684 year: 1984 ident: ref_31 article-title: Molecular Dynamics with Coupling to an External Bath publication-title: J. Chem. Phys. doi: 10.1063/1.448118 contributor: fullname: Berendsen – ident: ref_9 doi: 10.1186/1472-6882-5-22 – volume: 1–2 start-page: 19 year: 2015 ident: ref_27 article-title: GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers publication-title: SoftwareX doi: 10.1016/j.softx.2015.06.001 contributor: fullname: Abraham – volume: 38 start-page: 236 year: 1999 ident: ref_34 article-title: Peptide Folding: When Simulation Meets Experiment publication-title: Angew. Chem. Int. Ed. doi: 10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M contributor: fullname: Daura – volume: 33 start-page: 10026 year: 1994 ident: ref_12 article-title: Specific Nucleus as the Transition State for Protein Folding: Evidence from the Lattice Model publication-title: Biochemistry doi: 10.1021/bi00199a029 contributor: fullname: Abkevich – volume: 21 start-page: 3955 year: 1982 ident: ref_20 article-title: Orthogonal Packing of Beta-Pleated Sheets in Proteins publication-title: Biochemistry doi: 10.1021/bi00260a009 contributor: fullname: Chothia – volume: 32 start-page: W500 year: 2004 ident: ref_24 article-title: STRIDE: A Web Server for Secondary Structure Assignment from Known Atomic Coordinates of Proteins publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkh429 contributor: fullname: Heinig – volume: 75 start-page: 1258 year: 2010 ident: ref_21 article-title: Structures Closed into Cycles in Proteins Containing 3β-Corners publication-title: Biochem. Biokhimiia doi: 10.1134/S000629791010007X contributor: fullname: Boshkova – volume: 18 start-page: 1463 year: 1997 ident: ref_32 article-title: LINCS: A Linear Constraint Solver for Molecular Simulations publication-title: J. Comput. Chem. doi: 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H contributor: fullname: Hess – volume: 63 start-page: 1399 year: 2004 ident: ref_5 article-title: Long Term High Intensity Exercise and Damage of Small Joints in Rheumatoid Arthritis publication-title: Ann. Rheum. Dis. doi: 10.1136/ard.2003.015826 contributor: fullname: Munneke – volume: 36 start-page: 395 year: 2007 ident: ref_16 article-title: Conformational Dynamics and Ensembles in Protein Folding publication-title: Annu. Rev. Biophys. Biomol. Struct. doi: 10.1146/annurev.biophys.36.040306.132608 – volume: 284 start-page: 288 year: 1991 ident: ref_19 article-title: Structure of Coiled Beta-Beta-Hairpins and Beta-Beta-Corners publication-title: FEBS Lett. doi: 10.1016/0014-5793(91)80706-9 contributor: fullname: Efimov – volume: 40 start-page: 1175 year: 2001 ident: ref_10 article-title: A Vegan Diet Free of Gluten Improves the Signs and Symptoms of Rheumatoid Arthritis: The Effects on Arthritis Correlate with a Reduction in Antibodies to Food Antigens publication-title: Rheumatol. Oxf. Engl. doi: 10.1093/rheumatology/40.10.1175 contributor: fullname: Ringertz – volume: 3 start-page: 46 year: 2021 ident: ref_3 article-title: High Intensity Resistance Training as Intervention Method to Knee Osteoarthritis publication-title: Sports Med. Health Sci. doi: 10.1016/j.smhs.2021.02.005 contributor: fullname: Malorgio – volume: 166 start-page: 33 year: 1984 ident: ref_18 article-title: A Novel Super-Secondary Structure of Proteins and the Relation between the Structure and the Amino Acid Sequence publication-title: FEBS Lett. doi: 10.1016/0014-5793(84)80039-3 contributor: fullname: Efimov – volume: 1 start-page: 388 year: 1994 ident: ref_26 article-title: Structure of the Carboxy-Terminal LIM Domain from the Cysteine Rich Protein CRP publication-title: Nat. Struct. Biol. doi: 10.1038/nsb0694-388 contributor: fullname: Miles – volume: 298 start-page: 261 year: 1992 ident: ref_17 article-title: A Novel Super-Secondary Structure of β-Proteins A Triple-Strand Corner publication-title: FEBS Lett. doi: 10.1016/0014-5793(92)80072-O contributor: fullname: Efimov – volume: 47 start-page: W477 year: 2019 ident: ref_23 article-title: 2StrucCompare: A Webserver for Visualizing Small but Noteworthy Differences between Protein Tertiary Structures through Interrogation of the Secondary Structure Content publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkz456 contributor: fullname: Drew – volume: 20 start-page: 127 year: 2018 ident: ref_6 article-title: Ten Weeks of High-Intensity Interval Walk Training Is Associated with Reduced Disease Activity and Improved Innate Immune Function in Older Adults with Rheumatoid Arthritis: A Pilot Study publication-title: Arthritis Res. Ther. doi: 10.1186/s13075-018-1624-x contributor: fullname: Bartlett – volume: 8 start-page: 71 year: 2002 ident: ref_11 article-title: Effects of a Very Low-Fat, Vegan Diet in Subjects with Rheumatoid Arthritis publication-title: J. Altern. Complement. Med. doi: 10.1089/107555302753507195 contributor: fullname: McDougall – volume: 12 start-page: 20150876 year: 2015 ident: ref_1 article-title: Fold and Flexibility: What Can Proteins’ Mechanical Properties Tell Us about Their Folding Nucleus? publication-title: J. R. Soc. Interface doi: 10.1098/rsif.2015.0876 – volume: 115 start-page: 2081 year: 2015 ident: ref_4 article-title: The Effects of High Intensity Interval Training in Women with Rheumatic Disease: A Pilot Study publication-title: Eur. J. Appl. Physiol. doi: 10.1007/s00421-015-3186-9 contributor: fullname: Sandstad – volume: 18 start-page: 394 year: 1999 ident: ref_7 article-title: Decreased CD4+ Lymphocyte Activation and Increased Interleukin-4 Production in Peripheral Blood of Rheumatoid Arthritis Patients after Acute Starvation publication-title: Clin. Rheumatol. doi: 10.1007/s100670050125 contributor: fullname: Fraser – volume: 426 start-page: 884 year: 2003 ident: ref_13 article-title: Protein Folding and Misfolding publication-title: Nature doi: 10.1038/nature02261 contributor: fullname: Dobson – volume: 338 start-page: 899 year: 1991 ident: ref_8 article-title: Controlled Trial of Fasting and One-Year Vegetarian Diet in Rheumatoid Arthritis publication-title: Lancet Lond. Engl. doi: 10.1016/0140-6736(91)91770-U contributor: fullname: Haugen – volume: 4 start-page: 52 year: 2017 ident: ref_2 article-title: Managing Rheumatoid Arthritis with Dietary Interventions publication-title: Front. Nutr. doi: 10.3389/fnut.2017.00052 contributor: fullname: Khanna – volume: 126 start-page: 014101 year: 2007 ident: ref_30 article-title: Canonical Sampling through Velocity Rescaling publication-title: J. Chem. Phys. doi: 10.1063/1.2408420 contributor: fullname: Bussi – volume: 2 start-page: 285 year: 2011 ident: ref_29 article-title: Conformational Behavior of Stereo Regular Substituted Polyglycolides Is Side Chain Dependent publication-title: J. Biophys. Chem. doi: 10.4236/jbpc.2011.23033 contributor: fullname: Nandel – volume: 103 start-page: 8577 year: 1995 ident: ref_33 article-title: A Smooth Particle Mesh Ewald Method publication-title: J. Chem. Phys. doi: 10.1063/1.470117 contributor: fullname: Essmann |
| SSID | ssj0023259 |
| Score | 2.4166415 |
| Snippet | Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular... |
| SourceID | doaj pubmedcentral proquest crossref |
| SourceType | Open Website Open Access Repository Aggregation Database |
| StartPage | 10466 |
| SubjectTerms | Amino acids Arthritis Autoimmune diseases Autoimmunity Binding Binding sites Cell signaling Cytokine receptors Cytokines Exercise Globules Hydrophobicity Inflammatory diseases Isoforms JAK inhibitor Janus kinase Janus kinase 2 Kinases Ligands Molecular docking molecular modeling Molecular modelling Pathogenesis Physical fitness Proteins Rheumatoid arthritis ruxolitinib Selective binding Selectivity Synovitis |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEB7SQKGXkr6omzQoUHozsfXWcdMmpA30kG0h5GL0MnEh3pLdheTfZyR7l_iUS0-2JR3kGY9mPs8L4ItRJjjOfOkqpUpua1ta6VRJreSuDjxWdUpOPp-rX1f6-2kqk7Nt9ZViwobywAPhjltOPQqBbiuuuGHehjbIlktnPNr6ZgA-ld6AqRFqMZrbpNWofUopjByqazIE-Mfd39slGjU6OTflRBvlov0TS3MaJ_lE8ZztwevRYiSzYadvYCf2b-Hl0EPy4R1cz1YpsZjMu9uxExdZtATNOnLS5YyV9PhzdlET24d0Q0n695pXzHMTHDzvyI_-pnMo3Hfkcn2fQ-L6zr2HP2env7-dl2PDhNJzoVelaWtLdaitcqqqHItUR2rwNG658dyqQB2aP0Jqj9egW2-YFR6thIjDMXD2AXb7RR8_AqmEZ8FyVKGSIcMqGxk3TgbF6ki5CAV83RCu-TfUxWgQTyQKNxMKF3CSyLpdlMpZ5wFkcjMyuXmOyQUcbJjSjDK2bChCPSE0IsoCjrbTKB3J5WH7uFjnNcnTaKgqQE2YOdnQdKbvbnKdbSNwO0x--h9vsA-vaEqcSK4ocwC7q7t1_AwvlmF9mL_cR5P_8i4 priority: 102 providerName: Directory of Open Access Journals |
| Title | Atomic Simulation of the Binding of JAK1 and JAK2 with the Selective Inhibitor Ruxolitinib |
| URI | https://www.proquest.com/docview/2716558601 https://search.proquest.com/docview/2717684927 https://pubmed.ncbi.nlm.nih.gov/PMC9504736 https://doaj.org/article/f42c3768f047493cadfd6f46b9c87191 |
| Volume | 23 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1ba9RAFD64BcEXqTeMrcsI4lu6yVwyM4_b2tJaFHEVxJcwt9iImy17Af33nplNSvPqU5LJBIZz5vJ9OTeAt1pqbzlzuS2kzLkpTW4qK3NqKm5Lz0NRxuDky4X89F29P49pcsQQC5Oc9p1tT7rfy5OuvUm-lbdLNxv8xGafP55pUXDJqtkEJogNB4resyyGgH6fTJMhn5-1v5YbxDAq2jJjvSKG5xFl0a3w3jmU0vWPMObYQ_LekXNxCI97rEjm-zE9gQehewoP99Uj_z6DH_NtDCkmi3bZ1-Aiq4YgoCOnbYpViY8f5tclMZ2PN5TEv66pxyKVv8Gdjlx1N63FZb0mX3Z_kjNc19rn8O3i_OvZZd6XSsgdF2qb66Y0VPnSSCuLwrJAVaAa9-GGa8eN9NQi8BGVcnj1qnGaGeEQHwRsDp6zF3DQrbrwEkghHPOG4-FZMVRVYQLj2lZesjJQLnwG7wbB1bf7jBg1Moko7Hok7AxOo1jvOsVE1qlhtf5Z9-qsG04d7nGqQY1yzZzxja8aXlntkMrpMoPjQSl1v7o2NUWSJ4RCLpnBm7vXuC6iscN0YbVLfaKNUVOZgRwpczSg8RuccCnDdj_BXv33l0fwiMY4iWh50sdwsF3vwmuYbPxuirj96nqauP80zdx_D63y0Q |
| link.rule.ids | 230,315,729,782,786,866,887,2108,27935,27936,53803,53805 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB7RIgQX3hUpBYyEuKWb2E4cH7el1ZY-hNgiIS6RX6FBXW-1Dwn-PWNvUjXXnpLYjmR57Jn5PC-AT1JIqzkzqc6ESLnKVapKLVKqSq5zy12Wh-DkyVRc_Ky-HIU0OUUfCxOd9o1u9_31bN-3V9G38mZmRr2f2Ojb-aEsMi5YOdqCh3heM9aD9A5nMVTpN-k0GSL6UftntkQtpgrWzFCxiKFEoiw4Ft6RRDFh_0DLHPpI3hE6x8_uOd3n8LTTMsl40_0CHjj_Eh5t6k7-ewW_xqsQjEym7ayr3kXmDUFVkBy0McolfH4dn-ZEeRteKAn3tXHENBbOQR5JTvxVq5EhLMj39d_oRudb_Rp-HB9dHk7SrshCanhRrVLZ5IpWNldCiyzTzNHKUYkcvOHScCUs1agyFWVl8GmrxkimCoOahcNmZznbgW0_9-4NkKwwzCqOYrdkSORMOcalLq1guaO8sAl87he8vtnk0qgRgwQi1QMiJXAQyHE7KKTAjg3zxe-6W9m64dQgd6waXFwumVG2sWXDSy0NgkCZJ7DXE7PuzuWypggPi6JCFJrAx9tuPFHBTKK8m6_jmGCdlFQkIAabYDChYQ_SPubm7mi9e-8_P8DjyeX5WX12cnH6Fp7QEG0R7FdyD7ZXi7V7B1tLu34fd_x_YFgGfw |
| linkToPdf | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwEB7RIhAX3ohAASMhbmkS24nt4_axailUFQsS4hL5FRrEZlf7kODfM_ZmV80VTkmciWR57JlvMi-Ad0ooZzizqcmFSLkudKorI1KqK24Kx31ehOTks4m4_CZPTkOZnF2rrxi0b0172P2aHnbtdYytnE9tto0Ty64-Hasy54JV2dw12R7cxjObl1tDvbe1GML6TUlNhlZ91v6cLhHJyODRDF2LGGolykJw4Q1tFIv2D5DmME7yhuIZP_iPKT-E-z3aJKMNySO45bvHcGfTf_LPE_g-WoWkZDJpp30XLzJrCEJCctTGbJfw-GF0URDduXBDSfhvGykmsYEOykpy3l23BgXDgnxe_47hdF1rnsLX8emX47O0b7aQWl7KVaqaQlPpCi2MyHPDPJWeKpTkDVeWa-GoQehUVtLi1cnGKqZLiwjD47B3nD2D_W7W-edA8tIypzmq34ohs3PtGVemcoIVnvLSJfB-u-j1fFNTo0ZbJDCqHjAqgaPAkh1RKIUdB2aLH3W_unXDqUUpKRtcYK6Y1a5xVcMroywag6pI4GDL0Lo_n8uaoplYlhKt0QTe7l7jyQruEt352TrSBC-loiIBMdgIgwkN3yD_Y43unt8v_vnLN3D36mRcfzy_vHgJ92hIughuLHUA-6vF2r-CvaVbv46b_i-k9gj_ |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Atomic+Simulation+of+the+Binding+of+JAK1+and+JAK2+with+the+Selective+Inhibitor+Ruxolitinib&rft.jtitle=International+journal+of+molecular+sciences&rft.au=Kondratyev%2C+Maxim&rft.au=Rudnev%2C+Vladimir+R&rft.au=Nikolsky%2C+Kirill+S&rft.au=Stepanov%2C+Alexander+A&rft.date=2022-09-09&rft.eissn=1422-0067&rft.volume=23&rft.issue=18&rft_id=info:doi/10.3390%2Fijms231810466&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1422-0067&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1422-0067&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1422-0067&client=summon |