Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String
The quantitative structure−activity relationship (QSPR) model was formulated to quantify values of the binding constant (lnK) of a series of ligands to beta−cyclodextrin (β-CD). For this purpose, the multivariate adaptive regression splines (MARSplines) methodology was a...
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MDPI AG
2019-07-01
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| Series: | Symmetry |
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| Online Access: | https://www.mdpi.com/2073-8994/11/7/922 |
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| author | Piotr Cysewski Maciej Przybyłek |
| author_facet | Piotr Cysewski Maciej Przybyłek |
| author_sort | Piotr Cysewski |
| collection | DOAJ |
| description | The quantitative structure−activity relationship (QSPR) model was formulated to quantify values of the binding constant (lnK) of a series of ligands to beta−cyclodextrin (β-CD). For this purpose, the multivariate adaptive regression splines (MARSplines) methodology was adopted with molecular descriptors derived from the simplified molecular input line entry specification (SMILES) strings. This approach allows discovery of regression equations consisting of new non-linear components (basis functions) being combinations of molecular descriptors. The model was subjected to the standard internal and external validation procedures, which indicated its high predictive power. The appearance of polarity-related descriptors, such as XlogP, confirms the hydrophobic nature of the cyclodextrin cavity. The model can be used for predicting the affinity of new ligands to β-CD. However, a non-standard application was also proposed for classification into Biopharmaceutical Classification System (BCS) drug types. It was found that a single parameter, which is the estimated value of lnK, is sufficient to distinguish highly permeable drugs (BCS class I and II) from low permeable ones (BCS class II and IV). In general, it was found that drugs of the former group exhibit higher affinity to β-CD then the latter group (class III and IV). |
| first_indexed | 2024-04-11T18:19:15Z |
| format | Article |
| id | doaj.art-d3bcc665528a4228bb43268be292185a |
| institution | Directory Open Access Journal |
| issn | 2073-8994 |
| language | English |
| last_indexed | 2024-04-11T18:19:15Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Symmetry |
| spelling | doaj.art-d3bcc665528a4228bb43268be292185a2022-12-22T04:09:49ZengMDPI AGSymmetry2073-89942019-07-0111792210.3390/sym11070922sym11070922Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES StringPiotr Cysewski0Maciej Przybyłek1Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, PolandDepartment of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, PolandThe quantitative structure−activity relationship (QSPR) model was formulated to quantify values of the binding constant (lnK) of a series of ligands to beta−cyclodextrin (β-CD). For this purpose, the multivariate adaptive regression splines (MARSplines) methodology was adopted with molecular descriptors derived from the simplified molecular input line entry specification (SMILES) strings. This approach allows discovery of regression equations consisting of new non-linear components (basis functions) being combinations of molecular descriptors. The model was subjected to the standard internal and external validation procedures, which indicated its high predictive power. The appearance of polarity-related descriptors, such as XlogP, confirms the hydrophobic nature of the cyclodextrin cavity. The model can be used for predicting the affinity of new ligands to β-CD. However, a non-standard application was also proposed for classification into Biopharmaceutical Classification System (BCS) drug types. It was found that a single parameter, which is the estimated value of lnK, is sufficient to distinguish highly permeable drugs (BCS class I and II) from low permeable ones (BCS class II and IV). In general, it was found that drugs of the former group exhibit higher affinity to β-CD then the latter group (class III and IV).https://www.mdpi.com/2073-8994/11/7/922beta-cyclodextrinQSPRbinding constant |
| spellingShingle | Piotr Cysewski Maciej Przybyłek Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String Symmetry beta-cyclodextrin QSPR binding constant |
| title | Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String |
| title_full | Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String |
| title_fullStr | Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String |
| title_full_unstemmed | Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String |
| title_short | Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String |
| title_sort | predicting value of binding constants of organic ligands to beta cyclodextrin application of marsplines and descriptors encoded in smiles string |
| topic | beta-cyclodextrin QSPR binding constant |
| url | https://www.mdpi.com/2073-8994/11/7/922 |
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