LigBuilder V3: A Multi-Target de novo Drug Design Approach
With the rapid development of systems-based pharmacology and poly-pharmacology, method development for rational design of multi-target drugs has becoming urgent. In this paper, we present the first de novo multi-target drug design program LigBuilder V3, which can be used to design ligands to target...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00142/full |
| _version_ | 1818037114121486336 |
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| author | Yaxia Yuan Jianfeng Pei Luhua Lai Luhua Lai Luhua Lai |
| author_facet | Yaxia Yuan Jianfeng Pei Luhua Lai Luhua Lai Luhua Lai |
| author_sort | Yaxia Yuan |
| collection | DOAJ |
| description | With the rapid development of systems-based pharmacology and poly-pharmacology, method development for rational design of multi-target drugs has becoming urgent. In this paper, we present the first de novo multi-target drug design program LigBuilder V3, which can be used to design ligands to target multiple receptors, multiple binding sites of one receptor, or various conformations of one receptor. LigBuilder V3 is generally applicable in de novo multi-target drug design and optimization, especially for the design of concise ligands for protein targets with large difference in binding sites. To demonstrate the utility of LigBuilder V3, we have used it to design dual-functional inhibitors targeting HIV protease and HIV reverse transcriptase with three different strategy, including multi-target de novo design, multi-target growing, and multi-target linking. The designed compounds were computational validated by MM/GBSA binding free energy estimation as highly potential multi-target inhibitors for both HIV protease and HIV reverse transcriptase. The LigBuilder V3 program can be downloaded at “http://www.pkumdl.cn/ligbuilder3/”. |
| first_indexed | 2024-12-10T07:21:41Z |
| format | Article |
| id | doaj.art-9c7abdfd3b8444d0adcf5909b9a2d2a8 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-10T07:21:41Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-9c7abdfd3b8444d0adcf5909b9a2d2a82022-12-22T01:57:47ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-02-01810.3389/fchem.2020.00142508229LigBuilder V3: A Multi-Target de novo Drug Design ApproachYaxia Yuan0Jianfeng Pei1Luhua Lai2Luhua Lai3Luhua Lai4Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, ChinaCenter for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, ChinaBeijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, ChinaCenter for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, ChinaCenter for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, ChinaWith the rapid development of systems-based pharmacology and poly-pharmacology, method development for rational design of multi-target drugs has becoming urgent. In this paper, we present the first de novo multi-target drug design program LigBuilder V3, which can be used to design ligands to target multiple receptors, multiple binding sites of one receptor, or various conformations of one receptor. LigBuilder V3 is generally applicable in de novo multi-target drug design and optimization, especially for the design of concise ligands for protein targets with large difference in binding sites. To demonstrate the utility of LigBuilder V3, we have used it to design dual-functional inhibitors targeting HIV protease and HIV reverse transcriptase with three different strategy, including multi-target de novo design, multi-target growing, and multi-target linking. The designed compounds were computational validated by MM/GBSA binding free energy estimation as highly potential multi-target inhibitors for both HIV protease and HIV reverse transcriptase. The LigBuilder V3 program can be downloaded at “http://www.pkumdl.cn/ligbuilder3/”.https://www.frontiersin.org/article/10.3389/fchem.2020.00142/fullDe novo designMulti-target drug design (MTDD)multi-target drug optimizationDual-functional inhibitorsLigBuilder |
| spellingShingle | Yaxia Yuan Jianfeng Pei Luhua Lai Luhua Lai Luhua Lai LigBuilder V3: A Multi-Target de novo Drug Design Approach Frontiers in Chemistry De novo design Multi-target drug design (MTDD) multi-target drug optimization Dual-functional inhibitors LigBuilder |
| title | LigBuilder V3: A Multi-Target de novo Drug Design Approach |
| title_full | LigBuilder V3: A Multi-Target de novo Drug Design Approach |
| title_fullStr | LigBuilder V3: A Multi-Target de novo Drug Design Approach |
| title_full_unstemmed | LigBuilder V3: A Multi-Target de novo Drug Design Approach |
| title_short | LigBuilder V3: A Multi-Target de novo Drug Design Approach |
| title_sort | ligbuilder v3 a multi target de novo drug design approach |
| topic | De novo design Multi-target drug design (MTDD) multi-target drug optimization Dual-functional inhibitors LigBuilder |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00142/full |
| work_keys_str_mv | AT yaxiayuan ligbuilderv3amultitargetdenovodrugdesignapproach AT jianfengpei ligbuilderv3amultitargetdenovodrugdesignapproach AT luhualai ligbuilderv3amultitargetdenovodrugdesignapproach AT luhualai ligbuilderv3amultitargetdenovodrugdesignapproach AT luhualai ligbuilderv3amultitargetdenovodrugdesignapproach |