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In silico prediction of blood-brain barrier permeation using the calculated molecular cross-sectional area as main parameter

Gerebtzoff, G. and Seelig, A.. (2006) In silico prediction of blood-brain barrier permeation using the calculated molecular cross-sectional area as main parameter. Journal of Chemical Information and Modeling, Vol. 46, H. 6. pp. 2638-2650.

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Official URL: http://edoc.unibas.ch/dok/A5258460

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Abstract

The cross-sectional area, AD, of a compound oriented in an amphiphilic gradient such as the air-water or lipid-water interface has previously been shown to be crucial for membrane partitioning and permeation, respectively. Here, we developed an algorithm that determines the molecular axis of amphiphilicity and the cross-sectional area, ADcalc, perpendicular to this axis. Starting from the conformational ensemble of each molecule, the three-dimensional conformation selected as the membrane-binding conformation was the one with the smallest cross-sectional area, ADcalcM, and the strongest amphiphilicity. The calculated, ADcalcM, and the measured, AD, cross-sectional areas correlated linearly (n=55, slope, m=1.04, determination coefficient, r2=0.95). The calculated cross-sectional areas, ADcalcM, were then used together with the calculated octanol-water distribution coefficients, log D7.4, of the 55 compounds (with a known ability to permeate the blood-brain barrier) to establish a calibration diagram for the prediction of blood-brain barrier permeation. It yielded a limiting cross-sectional area (ADcalcM=70 A2) and an optimal range of octanol-water distribution coefficients (-1.4
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig A)
UniBasel Contributors:Seelig-Löffler, Anna
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:0095-2338
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:31

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