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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. October 2003, Volume 2, Number 10, 702-711 |
Computational Prediction of Drug-Albumin Binding Affinity by
Modeling Liquid Chromatographic Interactions
Toshihiko Hanai, Rie Miyazaki, Etsuko Kamijima, Hiroshi Homma, and Toshio Kinoshita
Internet Electron. J. Mol. Des. 2003, 2, 702-711
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Abstract:
A fast analytical method is required to measure human serum
albumin-drug binding affinity in drug discovery research. A
liquid chromatographic system was established without albumin
based on the conformational flexibility of the albumin molecule
and the basic molecular forces, ion-ion and hydrophobic
interactions, involved in the molecular recognition of albumin.
Using a computational chemical calculation to analyze liquid
chromatographic data, the direct interaction between a
model-phase and a drug was calculated as energy values with the MM2
calculation. Computational chemistry using a model adsorbent is
a new method for quantitative analysis of the retention of acidic
drugs on a guanidino phase which was used for ion-exchange
liquid chromatography of acidic drugs. Furthermore, the
computational chemical method demonstrated the possibility of
estimating albumin-acidic drug binding affinity without chemical
experiments. The r2 value was 0.922 (n = 13) between binding
affinity values (log nK) and interaction energy values of the final
structure (ΔFS).
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