Virtual filtering

This section presents the different methods employed as virtual filters to predict log P in the 1-octanol/water system and in other solvent systems. In Table 5.1, one can find a list of useful softwares which use one of the reviewed methods (Table 5.1). 

Virtual Filtering In Silica Prediction of log P and log D 93 Table 5.1 Non-exhaustive list of software packages which use one of the methods described. 

Permeability-molecular surface area-in vitro-in silico model The permeability values obtained from the Caco-2 cell monolayers have been traditionally used to devise in silico models for the prediction of drug absorption. In this paper, the use of molecular surface areas as descriptors of permeability and solubility will be reviewed. Moreover, a virtual filter for the prediction of oral drug developability based on the successful combination of in vitro and in silico models of drug permeability and aqueous drug solubility will be discussed. 

This concept involves two methodologies transformation of the master monochromator spectra to look like spectra from another instrument model, and standardization of spectra to look like spectra from the master instrument of the same model. Transformed spectra are said to come from a virtual instrument because the instrument from which the spectra appear to come did not produce the spectra. A monochromator can be configured as a virtual tilting or fixed filter instrument. These virtual filter instruments can be used as master instruments to which actual filter instruments are standardized. Both methods rely on the spectra of the standardization samples to characterize the instruments. 

Instmment standardization requires scanning the characterization samples with the master monochromator (as a virtual filter instmment) and the filter instrument to be standardized. 

Prediction of various physicochemical properties such as solubihty, lipophhicity log P, pfQ, number of H-donor and acceptor atoms, number of rotatable bonds, polar surface area), drug-likeness, lead-likeness, and pharmacokinetic properties (ADMET profile). These properties can be applied as a filter in the prescreening step in virtual screening. 

In general, the first step in virtual screening is the filtering by the application of Lipinski s Rule of Five [20]. Lipinski s work was based on the results of profiling the calculated physical property data in a set of 2245 compounds chosen from the World Drug Index. Polymers, peptides, quaternary ammonium, and phosphates were removed from this data set. Statistical analysis of this data set showed that approximately 90% of the remaining compounds had ... 

Rotary Vacuum Disk Filters. An alternative to the dmm filter is the disk filter, which uses a number of disks mounted vertically on a horizontal shaft and suspended in a slurry reservoir. This arrangement provides a greater surface area for a given floor space, by as much as a factor of 4, but cake washing is more difficult and cloth washing virtually impossible. 

Some PFBC boiler designs incorporate high-temperature, high-pressure (HTHP) filter devices in the flue-gas stream. These are installed primarily to protec t the gas turbine from erosion damage by the fine particles that escape the cyclones, but as the filters remove virtually all the suspended particulates, they also eliminate the need for back-end removal. The commonest HTHP filter elements used are rigid ceramic candles. 

The quaternary phosphonium salt is prepared by refluxing for 12 hours or longer a mixture of 4.5 g of benzyl chloride and 13 g of triphenylphosphine in 70 ml of xylene. On cooling to approx. 60°, colorless crystals of benzyltriphenylphosphonium chloride can be filtered off, washed with xylene (approx. 50 ml) and dried. The yield is virtually quantitative, mp 310-311°. 

Some 70-85 per cent of failures and wear problems in lubricated machines are caused by oil contamination. Clean oil extends machine and oil life and gives greater reliability, higher productivity and lower maintenance cost. Hence, some type of filter is an essential part of virtually all lubrication systems. 

Visual methods have been virtually displaced for most determinations by methods depending upon the use of photoelectric cells (filter photometers or absorptiometers, and spectrophotometers), thus leading to reduction of the experimental errors of colorimetric determinations. The so-called photoelectric colorimeter is a comparatively inexpensive instrument, and should be available in every laboratory. The use of spectrophotometers has enabled determinations to be extended into the ultraviolet region of the spectrum, whilst the use of chart recorders means that the analyst is not limited to working at a single fixed wavelength. 

In general, the described techniques provide an effective, flexible, and relatively fast solution for library design based on analysis of bioscreening data. The quantitative relationships, based on the assessment of contribution values of various molecular descriptors, not only permit the estimation of potential biological activity of candidate compounds before synthesis but also provide information concerning the modification of the structural features necessary for this activity. Usually these techniques are applied in the form of computational filters for constraining the size of virtual combinatorial libraries and... 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

Wolber G, Langer T LigandScout 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. / Chem Inf Model 2005 45 160-9. 

All of these parameters (with the possible exception of SAP) are frequently used in QSAR studies or as filters in virtual screening. The SAP descriptor was included to check for correlations between PSA and quantum chemically calculated charges. 

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