Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration
Abstract Enzyme inhibition analysis is essential in drug development and food processing, necessitating precise estimation of inhibition constants. Traditionally, these constants are estimated through experiments using multiple substrate and inhibitor concentrations, but inconsistencies across studi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60468-z |
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| author | Hyeong Jun Jang Yun Min Song Jang Su Jeon Hwi-yeol Yun Sang Kyum Kim Jae Kyoung Kim |
| author_facet | Hyeong Jun Jang Yun Min Song Jang Su Jeon Hwi-yeol Yun Sang Kyum Kim Jae Kyoung Kim |
| author_sort | Hyeong Jun Jang |
| collection | DOAJ |
| description | Abstract Enzyme inhibition analysis is essential in drug development and food processing, necessitating precise estimation of inhibition constants. Traditionally, these constants are estimated through experiments using multiple substrate and inhibitor concentrations, but inconsistencies across studies highlight a need for a more systematic approach to set experimental designs across all types of enzyme inhibition. Here, we address this by analyzing the error landscape of estimations in various experimental designs. We find that nearly half of the conventional data is dispensable and even introduces bias. Instead, by incorporating the relationship between IC50 and inhibition constants into the fitting process, we find that using a single inhibitor concentration greater than IC50 suffices for precise estimation. This IC50-based optimal approach, which we name 50-BOA, substantially reduces (>75%) the number of experiments required while ensuring precision and accuracy. Additionally, we provide a user-friendly package that implements the 50-BOA. |
| format | Article |
| id | doaj-art-b1d29c258243433dbb70f13c4388c03f |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b1d29c258243433dbb70f13c4388c03f2025-08-20T02:05:38ZengNature PortfolioNature Communications2041-17232025-06-0116111410.1038/s41467-025-60468-zOptimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentrationHyeong Jun Jang0Yun Min Song1Jang Su Jeon2Hwi-yeol Yun3Sang Kyum Kim4Jae Kyoung Kim5School of Transdisciplinary Studies, KAISTBiomedical Mathematics Group, Pioneer Research Center for Mathematical and Computational Sciences, Institute for Basic ScienceCollege of Pharmacy, Chungnam National UniversityCollege of Pharmacy, Chungnam National UniversityCollege of Pharmacy, Chungnam National UniversityBiomedical Mathematics Group, Pioneer Research Center for Mathematical and Computational Sciences, Institute for Basic ScienceAbstract Enzyme inhibition analysis is essential in drug development and food processing, necessitating precise estimation of inhibition constants. Traditionally, these constants are estimated through experiments using multiple substrate and inhibitor concentrations, but inconsistencies across studies highlight a need for a more systematic approach to set experimental designs across all types of enzyme inhibition. Here, we address this by analyzing the error landscape of estimations in various experimental designs. We find that nearly half of the conventional data is dispensable and even introduces bias. Instead, by incorporating the relationship between IC50 and inhibition constants into the fitting process, we find that using a single inhibitor concentration greater than IC50 suffices for precise estimation. This IC50-based optimal approach, which we name 50-BOA, substantially reduces (>75%) the number of experiments required while ensuring precision and accuracy. Additionally, we provide a user-friendly package that implements the 50-BOA.https://doi.org/10.1038/s41467-025-60468-z |
| spellingShingle | Hyeong Jun Jang Yun Min Song Jang Su Jeon Hwi-yeol Yun Sang Kyum Kim Jae Kyoung Kim Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration Nature Communications |
| title | Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration |
| title_full | Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration |
| title_fullStr | Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration |
| title_full_unstemmed | Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration |
| title_short | Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration |
| title_sort | optimizing enzyme inhibition analysis precise estimation with a single inhibitor concentration |
| url | https://doi.org/10.1038/s41467-025-60468-z |
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