MolSurf

Norinder, U., Osterberg, T., Arturs-son, P., Theoretical calculation and prediction of Caco-2 cell permeability using MolSurf parametrization and PLS statistics, Pharm. Res. 1997, 24, 1786-1791. 

MolSurf parameters [33] are descriptors derived from quantum mechanical calculations. These descriptors are computed at a surface of constant electron density, with which a very fine description of the properties of a molecule at the Van der Waals surface can be obtained. They describe various electrostatic properties such as hydrogen-bonding strengths and polarizability, as well as Lewis base and acid strengths. MolSurf parameters are computed using the following protocol. 

It is possible to derive a statistically good and predictive model for intestinal absorption using the MolSurf parameters (r2 = 0.916, q2 = 0.798). 

Another possible advantage with MolSurf descriptors (and also other multi parameter descriptors) is the fact that they describe the investigated compounds not only with a single value, as in the case of PSA and log P descriptors, but in a multivariate way. This approach provides a more balanced description of the requirements that a structure must have in order to be well absorbed and may, in turn, provide additional insight on how to develop compounds having favorable absorption properties. However, as will be described in Section 16.4.10, simpler -i.e., less computationally demanding - parameters carrying similar information content with equal interpretability may be used to derive models for intestinal absorption at the same level of statistical quality. 

MolSurf version 3.10, Q. A., Hertig Carls Alle 29, SE-691 41, Karlskoga, Sweden, (e-mail qemist swipnet.se). 

Osterberg and Norinder [42] further analyzed a subset of the ATPase data published by Litman et al. [39]. The ATPase activity values were correlated by multivariate statistics with calculated descriptors (MolSurf descriptors) related to physicochemical properties suchaslipophilicity, polarity, polarizability and hydrogen bonding. After exclusion of one outlier and large molecules such as valinomycin, gramicidin S and so on, which were not handled by the MolSurf software, only 21 compounds were included in the study. Two models were derived model 1, based on... 

Norinder, U, Osterberg, T. and Artursson, P. (1997). Theoretical Calculation and Prediction of CACO-2 Cell Permeability Using MolSurf Pmametrization and PLS Statistics. Pharm.Res., 14, 1786-1791. 

Norinder, U., Sjoberg, P. and Osterberg, T. (1998). Theoretical Calculation and Prediction of Brain-Blood Partitioning of Organic Solutes Using MolSurf Parametrization and PLS Statistics. J.Pharm.Sci., 87,952-959. 

Norinder U, Osterberg T, Artursson P. Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parameterization and PLS statistics. Eur J Pharm Sci 1999 8 49-56. 

Norinder U, Sjoberg P, Osterberg T. Theoretical calculation and prediction of brain-blood partitioning of organic solutes using molsurf parameterization and PLS statistics. J Pharm Sci 1998 87 952-9. 

Norinder, U. Osterberg, T Artursson,P. Theoretical Calculation andPrediction of Intestinal Absoqttion of Drugs in Human Using MolSurf Parametrization and PLS Statistics, Eur. J. Pharm. Sci. 8,49-56 (1999). 

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