Fragment based systems

The program system COBRA [118, 119] can be regarded as a rule- and data-based approach, but also applies the principles of fragment-based (or template-based) methods extensively (for a detailed description sec Chapter 11, Sections 7.1 and 7.2 in the Handbook). COBRA uses a library of predefined, optimized 3D molecular fragments which have been derived from crystal structures and foi ce-field calculations. Each fi agment contains some additional information on... 

The biochemical MS assay performance was studied for various biotin derivatives, such as biotin [m/z 245), N-biotinyl-6-aminocaproic acid hydrazide (m/z 372), biotin-hydrazide (m/z 259), N-biotinyl-L-lysine (m/z 373) and biotin-N-succinimi-dylester m/z 342). These five different bioactive compounds were consecutively injected into the biochemical MS assay. Figure 5.12 shows triplicate injections in the biochemical MS-based system of the different active compounds. Each compound binds to streptavidin, hence the MS responses of peaks of the reporter ligand (fluorescein-biotin, m/z 390) are similar. The use of SIM allows specific components to be selected and monitored, e.g. protonated molecule of the biotin derivatives. In this case, no peaks were observed for biotin-N-succinimidylester (m/z 342), because under the applied conditions fragmentation occurred to m/z 245. In combination with full-scan MS measurements, the molecular mass of active compounds can be determined simultaneously to the biochemical measurement. 

The representation is unambiguous since it corresponds to one and only one substance, but it is not unique because alternative numberings of the connection table would result in different representations for the same chemical substance (the connection table representation is discussed in more detail below). In addition to being categorized according to their uniqueness and ambiguity, chemical substance representations commonly used within computer-based systems can be further classified as systematic nomenclature, fragment codes, linear notations, connection tables, and coordinate representations. 

Complexes may also be constructed of a fusion of open fragments. For 7 this can lead to the well-known cubane class of complexes 15 (Table V). The cubane core is a structure found naturally in biological systems having E = S and metal fragments based upon Fe and/or Mo. Organometallic... 

In the Maximum Dissimilarity (MD) selection method described by Lajiness [40] the first compound is selected at random and subsequent compounds are then chosen iteratively, such that the distance to the nearest of the compounds already chosen is a maximum. This method is known as MaxMin. In this study, the compounds were represented by COUSIN 2-D fragment-based bitstrings. Polinsky et al. [41] use a similar algorithm in the LiBrain system. In this case, the molecules are represented by a feature vector that contains information about the following affinity types—aliphatic hydrophobic, aromatic hydrophobic, basic, acidic, hydrogen bond donor, hydrogen bond acceptor and polarizable heteroatom. 

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