Combined similarity and QSPR virtual screening for guest molecules of β-cyclodextrin

“…Quantitative structure-activity relationship (QSPR) methodology has been extensively used for evaluating the formation abilities of molecular complexes, and characterizing their properties [4,[29][30][31][32][33][34][35][36][37][38]. Cyclodextrin binding constant modeling deserves special attention due to its practical importance.…”

Section: Introductionmentioning

confidence: 99%

Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String

Cysewski

Przybyłek

2019

Symmetry

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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).

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Combined similarity and QSPR virtual screening for guest molecules of β-cyclodextrin

Cited by 6 publications

References 31 publications

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

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Predicting Value of Binding Constants of Organic Ligands to Beta-Cyclodextrin: Application of MARSplines and Descriptors Encoded in SMILES String

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