Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies
•Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands. Galectin...
Gespeichert in:
| Veröffentlicht in: | Journal of molecular graphics & modelling 2017-01, Vol.71, p.211-217 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 217 |
|---|---|
| container_issue | |
| container_start_page | 211 |
| container_title | Journal of molecular graphics & modelling |
| container_volume | 71 |
| creator | Walker, Alice R. Bonomi, Robin Popov, Vadim Gelovani, Juri G. Andrés Cisneros, G. |
| description | •Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands.
Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity. |
| doi_str_mv | 10.1016/j.jmgm.2016.10.018 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1880035072</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1093326316301851</els_id><sourcerecordid>1859470519</sourcerecordid><originalsourceid>FETCH-LOGICAL-c422t-69ac5ccb8e4a3c939b68605600ce8745675bcdc872db9d1342087c63dc3aea833</originalsourceid><addsrcrecordid>eNqNkU1rGzEQhkVIaNy0fyCHoGMu6-pjV9JCL8WkTSDQS3oW2tHYlrMfqbTr4H9fLXZ7LD5pmHnel9G8hNxytuSMqy-75a7bdEuR69xYMm4uyIIbLYtSlPIy16yWhRRKXpOPKe0YY9Iw_YFcC13LupZyQeCp32Maw8aNod9QcLEZtgcf3Yi0cQk9bfOs94muh0g3rkXIYCHpexi31A_wOssyQLshz6bWReoPvesCJJrGyQdMn8jV2rUJP5_eG_Lr-8PL6rF4_vnjafXtuYBSiLFQtYMKoDFYOgl5wUYZxSrFGKDRZaV01YAHo4Vvas9lKZjRoKQH6dAZKW_I_dH3LQ6_p_wr24UE2Laux2FKlhuTL1AxLc5Aq7rUrOL1OahQqlRcZ1QcUYhDShHX9i2GzsWD5czOkdmdnSOzc2RzL0eWRXcn_6np0P-T_M0oA1-PAObb7QNGmyBgD-hDzGlYP4T_-f8BMv-nyg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1852664617</pqid></control><display><type>article</type><title>Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Walker, Alice R. ; Bonomi, Robin ; Popov, Vadim ; Gelovani, Juri G. ; Andrés Cisneros, G.</creator><creatorcontrib>Walker, Alice R. ; Bonomi, Robin ; Popov, Vadim ; Gelovani, Juri G. ; Andrés Cisneros, G.</creatorcontrib><description>•Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands.
Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.</description><identifier>ISSN: 1093-3263</identifier><identifier>EISSN: 1873-4243</identifier><identifier>DOI: 10.1016/j.jmgm.2016.10.018</identifier><identifier>PMID: 27939933</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Affinity ; Binding energy ; Binding Sites ; Cancer ; Carbohydrate based ligands ; Carbohydrates ; Carbohydrates - chemistry ; Docking ; Galectin 3 - chemistry ; Galectin-3 ; Humans ; Ligands ; Molecular Docking Simulation ; Molecular dynamics ; Molecular Dynamics Simulation ; Positron emission ; Positron-Emission Tomography ; Protein Binding ; Protein Conformation ; Thermodynamics</subject><ispartof>Journal of molecular graphics & modelling, 2017-01, Vol.71, p.211-217</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-69ac5ccb8e4a3c939b68605600ce8745675bcdc872db9d1342087c63dc3aea833</citedby><cites>FETCH-LOGICAL-c422t-69ac5ccb8e4a3c939b68605600ce8745675bcdc872db9d1342087c63dc3aea833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jmgm.2016.10.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27939933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walker, Alice R.</creatorcontrib><creatorcontrib>Bonomi, Robin</creatorcontrib><creatorcontrib>Popov, Vadim</creatorcontrib><creatorcontrib>Gelovani, Juri G.</creatorcontrib><creatorcontrib>Andrés Cisneros, G.</creatorcontrib><title>Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies</title><title>Journal of molecular graphics & modelling</title><addtitle>J Mol Graph Model</addtitle><description>•Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands.
Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.</description><subject>Affinity</subject><subject>Binding energy</subject><subject>Binding Sites</subject><subject>Cancer</subject><subject>Carbohydrate based ligands</subject><subject>Carbohydrates</subject><subject>Carbohydrates - chemistry</subject><subject>Docking</subject><subject>Galectin 3 - chemistry</subject><subject>Galectin-3</subject><subject>Humans</subject><subject>Ligands</subject><subject>Molecular Docking Simulation</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Positron emission</subject><subject>Positron-Emission Tomography</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Thermodynamics</subject><issn>1093-3263</issn><issn>1873-4243</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1rGzEQhkVIaNy0fyCHoGMu6-pjV9JCL8WkTSDQS3oW2tHYlrMfqbTr4H9fLXZ7LD5pmHnel9G8hNxytuSMqy-75a7bdEuR69xYMm4uyIIbLYtSlPIy16yWhRRKXpOPKe0YY9Iw_YFcC13LupZyQeCp32Maw8aNod9QcLEZtgcf3Yi0cQk9bfOs94muh0g3rkXIYCHpexi31A_wOssyQLshz6bWReoPvesCJJrGyQdMn8jV2rUJP5_eG_Lr-8PL6rF4_vnjafXtuYBSiLFQtYMKoDFYOgl5wUYZxSrFGKDRZaV01YAHo4Vvas9lKZjRoKQH6dAZKW_I_dH3LQ6_p_wr24UE2Laux2FKlhuTL1AxLc5Aq7rUrOL1OahQqlRcZ1QcUYhDShHX9i2GzsWD5czOkdmdnSOzc2RzL0eWRXcn_6np0P-T_M0oA1-PAObb7QNGmyBgD-hDzGlYP4T_-f8BMv-nyg</recordid><startdate>201701</startdate><enddate>201701</enddate><creator>Walker, Alice R.</creator><creator>Bonomi, Robin</creator><creator>Popov, Vadim</creator><creator>Gelovani, Juri G.</creator><creator>Andrés Cisneros, G.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SC</scope><scope>7U5</scope><scope>JQ2</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope></search><sort><creationdate>201701</creationdate><title>Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies</title><author>Walker, Alice R. ; Bonomi, Robin ; Popov, Vadim ; Gelovani, Juri G. ; Andrés Cisneros, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-69ac5ccb8e4a3c939b68605600ce8745675bcdc872db9d1342087c63dc3aea833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Affinity</topic><topic>Binding energy</topic><topic>Binding Sites</topic><topic>Cancer</topic><topic>Carbohydrate based ligands</topic><topic>Carbohydrates</topic><topic>Carbohydrates - chemistry</topic><topic>Docking</topic><topic>Galectin 3 - chemistry</topic><topic>Galectin-3</topic><topic>Humans</topic><topic>Ligands</topic><topic>Molecular Docking Simulation</topic><topic>Molecular dynamics</topic><topic>Molecular Dynamics Simulation</topic><topic>Positron emission</topic><topic>Positron-Emission Tomography</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walker, Alice R.</creatorcontrib><creatorcontrib>Bonomi, Robin</creatorcontrib><creatorcontrib>Popov, Vadim</creatorcontrib><creatorcontrib>Gelovani, Juri G.</creatorcontrib><creatorcontrib>Andrés Cisneros, G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>ProQuest Computer Science Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><jtitle>Journal of molecular graphics & modelling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walker, Alice R.</au><au>Bonomi, Robin</au><au>Popov, Vadim</au><au>Gelovani, Juri G.</au><au>Andrés Cisneros, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies</atitle><jtitle>Journal of molecular graphics & modelling</jtitle><addtitle>J Mol Graph Model</addtitle><date>2017-01</date><risdate>2017</risdate><volume>71</volume><spage>211</spage><epage>217</epage><pages>211-217</pages><issn>1093-3263</issn><eissn>1873-4243</eissn><abstract>•Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands.
Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27939933</pmid><doi>10.1016/j.jmgm.2016.10.018</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1093-3263 |
| ispartof | Journal of molecular graphics & modelling, 2017-01, Vol.71, p.211-217 |
| issn | 1093-3263 1873-4243 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1880035072 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Affinity Binding energy Binding Sites Cancer Carbohydrate based ligands Carbohydrates Carbohydrates - chemistry Docking Galectin 3 - chemistry Galectin-3 Humans Ligands Molecular Docking Simulation Molecular dynamics Molecular Dynamics Simulation Positron emission Positron-Emission Tomography Protein Binding Protein Conformation Thermodynamics |
| title | Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T03%3A28%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Investigating%20carbohydrate%20based%20ligands%20for%20galectin-3%20with%20docking%20and%20molecular%20dynamics%20studies&rft.jtitle=Journal%20of%20molecular%20graphics%20&%20modelling&rft.au=Walker,%20Alice%20R.&rft.date=2017-01&rft.volume=71&rft.spage=211&rft.epage=217&rft.pages=211-217&rft.issn=1093-3263&rft.eissn=1873-4243&rft_id=info:doi/10.1016/j.jmgm.2016.10.018&rft_dat=%3Cproquest_cross%3E1859470519%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1852664617&rft_id=info:pmid/27939933&rft_els_id=S1093326316301851&rfr_iscdi=true |