Parallel in silico

As already outlined above, P-glycoprotein is constitutively expressed in several organs, such as kidney, liver, intestine, and also at the blood-brain barrier. P-gp substrates therefore show poor oral absorption, enhanced renal and biliary excretion, and usually do not enter the brain [28]. This spurred the development of medium- and high-throughput systems addressing the P-gp substrate properties of compounds of interest. These systems mostly rely on transport studies through a monolayer of P-gp expressing Caco-2 [29] or MDCK cells [30]. In parallel, in silico methods have also... 

B. What is the difference III. DATA MINING METHODS using parallel in silico... 

C. Assessing affinity profiles using parallel in silico screening... 

While this approach still requires the melting temperature of the substance in question, that is, requires its existence, the full in silico calculation based on the structural formula is now possible. Several recent publications present computational programs for the prediction of solubility. These approaches are being used for the pre-screening of candidates in advance of their synthesis, or for the design of combinatorial libraries. In a review of the different methodologies and the quality of results obtained from the most useful procedures it is concluded that viable procedures now exist for the determination of solubility with less than 1 log unit uncertainty. This uncertainty is judged to be adequate for use in the above processes. In parallel with this, combination of a newly miniaturized shake flask experimental method and a computational approach for solubility prediction has been published. ... 

Overall, PBPK models can provide insight into the several aspects associated with the kinetics of a drug within the human body, collectively termed as ADMET, for absorption, distribution, metabohsm, elimination, and toxicity. An application of the PBPK models at the early stage of drug development can be useful to rapidly screen candidate drugs based on their PK properties via in silico approaches (3,4). Due to the rapid increases in the computational power, and the parallel advances in the PBPK area, the role of PBPK models in pharmacometrics is likely to substantially increase. 

Janaki, C., and R. R. Joshi. 2003. Accelerating comparative genomics using parallel computing. In Silico Biol 3 429-40. 

Integrated systems suitable for processing the sometimes quite complex workflows more easily or automatically and to optimize new compounds in parallel for their potency, selectivity, and ADMET profile have to be developed. The reliability of the in silico models will be improved and their scope for predictions will be broader as soon as more reliable experimental data are available. However, there is the paradox of predictivity versus diversity. The greater the chemical diversity in a dataset. 

---