Selection DBCS

Dissimilarity-Based Compound Selection (DBCS) involves identifying directly the subset comprising the n most dissimilar compounds in a database containing N compounds, where typically n< N. Identification of the most dissimilar subset is not computationally feasible since it requires consideration... 

Local anesthetics are positively charged amphiphiles in solution. We have selected hydrochlorides of dibucaine (DBC H ), procaine (PRC H ), tetracaine (TTC H ), and lido-caine (LDC H ). All of these drugs are structurally similar they consist of the substituted benzene ring and tertiary amine moieties, as shown by (VI)-(IX) in Fig. 1. The presence of the positive charge increases the solubility in water and in consequence, the anesthetic efficiency. 

The default installation of Capture CIS uses a small database named BENCHACC.DBC. We need to change the database to our Digikey database. Select the BfUWSe button ... 

We are looking for the file named Digikey SC.dbc. This file is located in the CaptureVDatabase directory of the Oread Lite installation directory. Locate and select this file ... 

The basic DBCS algorithm has time complexity 0(n2N), where n compounds are selected from N. Since n is generally a small fraction of N, the time is thus cubic in N. DBCS can also be very computational demanding however, fast implementations have been developed, for example the MaxSum method described by Holliday et al. [42] and a MaxMin method described by Agrafiotis and Lobanov that can be used with low-dimensional descriptors [55],... 

Stereoselective bromiuation of olefins. Exclusive trans-addition of bromine to alkenes can be effected with this bromine-crown ether complex. Thus cis- and trans-jB-methylstyrene react with DBC-Brj to yield threo- and erylftro-l-phenyl-1,2-dibromopropane, respectively. Other brominating agents (Brj, PyBrj) are significantly less selective for this reaction. ... 

Figure 2 The selection of a subset of five diverse compounds using DBCS.

Given the large variety of molecular descriptors that exist, several approaches have been taken to evaluate which descriptors are most suitable for virtual screening although, to some extent, the choice of descriptors and subset selection method is interlinked. For example, as already mentioned, cell-based approaches are only appropriate for low-dimensional chemistry space whereas both DBCS and clustering can be used with high-dimensional data such as fingerprints. 

Several product-based approaches to library design that do not require full enumeration have been developed. Pickett et al. have described the design of a diverse amide library where diversity is measured in product space. The DIVSEL program is a DBCS method where dissimilarity is measured in three-point pharmacophore space [83]. Initially, 11 amines were selected based on maximum pharmacophore diversity. Then a total of 1100 carboxylic acids were identified following substructure searching. A set of 1100 pharmacophores keys was generated, where each key corresponds to one acid combined with the 11 amines. DIVSEL was used to select 100 acids based on the diversity of the products. The final library was found to cover 85% of the pharmacophores represented by the entire 12,100 virtual libraries. 

Partitioning methods are more efficient compound selection methods than clustering and DBCS they also have the advantage of being data independent, which means they can be used for rapid database/library comparisons, and they can be used to identify those areas of structural space that are underrepresented, which can be useful to identify areas of space (e.g., pharmacophore space) that are not covered by a library. Diverse subsets can easily be chosen by selecting compounds from each partition. 

The braze may be applied in the form of a paste, a powder, or a film. The combination is heated to the melting point of the selected braze in a vacuum to minimize oxidation of the copper. The active metal forms a hquidus with the oxygen in the system that acts to bond the metal to the ceramic. After brazing, the copper film may be processed in much the same manner as DBC. 

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