Dynamic PSA

Since experimental determination of intestinal absorption is quite demanding, Caco-2 cell monolayers have been successfully used to model passive drug absorption. Several models for the prediction of Caco-2 permeability using PSA were developed, including those of van de Waterbeemd et al. [5] and Palm et al. [22] who found that relationships between Caco-2 permeability and PSA is stronger than with Clog D, Krarup et al. [23] who used dynamic PSA calculated for water accessible molecular surface and Bergstrom et al. [24]. 

Using small datasets we initially showed that the dynamic PSA (PSABoltzman distribution of all low-energy conformations of the... 

Osterberg and Norinder [35] analyzed the improvement in the prediction of drug transport processes by the combination of the hydrogen-bonding descriptors and calculated log P. Two data sets were used. The calculated static PSA and the experimental log BB values for 70 compounds (data set 1) were taken from the work of Clark. The calculated dynamic PSA and the experimental log... 

This equation relies on a PSA value generated from a single conformer. More recent methods include variations from Feher et al, and Kelder et al, the latter group proposed a more direct correlation between Log BB and a so-called dynamic PSA (dPSA). The dPSA is challenging to obtain, since it is determined from a Boltzmann-weighted ensemble of molecular conformations. Note that, in Kelder et al. s formulation of Log BB, c Log P is not considered at all ... 

The dynamic PSA, PSAd, was developed by Palm et al. [73]. PSAd is calculated by a Monte Carlo conformational search with subsequent energy minimization. 

Devooght J., Smidts C. 1996. Probabilistic dynamics as a tool for dynamic PSA. In Reliability Engineering and System Safety (52) 185-196. 

IDPSA—frequently also called Dynamic PSA— can be regarded as a complementary analysis to the classical Deterministic (DSA) and ProbabiUs-tic (PSA) Safety Analyses (Adolfsson et al. 2011, Adolfsson et al. 2012). It makes extensive use of a deterministic dynamics code and applies advanced methods for an improved modeling and probabiUs-tic assessment of complex systems with significant process/hardware/software/firmware/human interaction (Aldemir 2013). An IDPSA is particularly suitable in the frame of a fire PSA, since it can more realistically model and assess the interaction of the fire dynamics with the performance of technical systems and human actions. 

Kloos, M. et al. 2013b. Updates and current application of the MCDET simulation tool for Dynamic PSA. In Proceedings of ANS PSA 2013 International Topical Meeting on Probabilistic Safety Assessment and Analysis Columbia, SC. 

Sundarmurthi Smidts, 2013 Data-driven BBNs for incorporation into dynamic PSA models. BBN used also as diagnostic tool for identifying the PSF combinations that most prominently occur in accidents involving human error. PSFA... 

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