Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities
Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3698 |
| _version_ | 1797212488464334848 |
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| author | Marina Gorostiola González Pepijn R. J. Rakers Willem Jespers Adriaan P. IJzerman Laura H. Heitman Gerard J. P. van Westen |
| author_facet | Marina Gorostiola González Pepijn R. J. Rakers Willem Jespers Adriaan P. IJzerman Laura H. Heitman Gerard J. P. van Westen |
| author_sort | Marina Gorostiola González |
| collection | DOAJ |
| description | Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of “wet-lab” experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets. |
| first_indexed | 2024-04-24T10:43:11Z |
| format | Article |
| id | doaj.art-3fa34ac451034cf5b0ad007a8dfa1c00 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:11Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3fa34ac451034cf5b0ad007a8dfa1c002024-04-12T13:19:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257369810.3390/ijms25073698Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and OpportunitiesMarina Gorostiola González0Pepijn R. J. Rakers1Willem Jespers2Adriaan P. IJzerman3Laura H. Heitman4Gerard J. P. van Westen5Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsLeiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsLeiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsLeiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsLeiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsLeiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsCancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of “wet-lab” experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets.https://www.mdpi.com/1422-0067/25/7/3698computational drug discoverymembrane proteincanceranticancer targetreceptor tyrosine kinaseRTK |
| spellingShingle | Marina Gorostiola González Pepijn R. J. Rakers Willem Jespers Adriaan P. IJzerman Laura H. Heitman Gerard J. P. van Westen Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities International Journal of Molecular Sciences computational drug discovery membrane protein cancer anticancer target receptor tyrosine kinase RTK |
| title | Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities |
| title_full | Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities |
| title_fullStr | Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities |
| title_full_unstemmed | Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities |
| title_short | Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities |
| title_sort | computational characterization of membrane proteins as anticancer targets current challenges and opportunities |
| topic | computational drug discovery membrane protein cancer anticancer target receptor tyrosine kinase RTK |
| url | https://www.mdpi.com/1422-0067/25/7/3698 |
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