BCUT chemistry-space

Mason, J.S. and Beno, B.R. Library design using BCUT chemistry-space descriptors and multiple four-point pharmacophore fingerprints simultaneous optimization and structure-based diversity. /. Mol. 

Although it is ubiquitous in chemoinformatics applications, the term vector should be used with caution as vectors are properly the objects of vector spaces and must satisfy the axioms of vector spaces. For example, vectors in BCUT chemistry spaces do not form a vector space because the sum of two BCUT vectors may not lie in the space (29). However, as long as this rather fine distinction is borne in mind, significant problems should not arise, and the term vector, taken in its broadest sense, will be used here. 

The receptor relevance of BCUT descriptors has inspired several groups to apply them in conjunction with other methods. Beno and Mason reported the use of simulated annealing to optimize library design using BCUT chemistry space and four-point pharmacophores concurrently (33) and the use of chemistry spaces in conjunction with property profiles (52). The application of such composite methods to target class library design is readily apparent. Pirard and Pickett reported the application of the chemometric method, partial least squares discriminant analysis, with BCUT descriptors to successfully classify ATP-site-directed kinase inhibitors active against five different protein kinases... 

The use of receptor-relevant BCUT chemistry spaces from DiverseSolutions (DVS) [15-19] is discussed in section 3.1. This involves the use of a subset of descriptors (atomic/molecular properties) determined to be relevant to discriminate the diversity of a large set of molecules. This method, reported by Pearlman and Smith [19], can be considered as a type of relative similarity and diversity, where the subset of properties that are... 

A recent modification to the method has been reported [18] that involves the use of a subset of the dimensions for a set of structures with similar biological activity. This subset from an activity-seeded structure-based clustering has been called the receptor-relevant BCUT chemistry-space, and was used to perform a number of validation studies [18, 19]. The... 

Figure 8 illustrates the occupied cells reported [11, 13] for the reference databases using a six dimensional BCUT chemistry space and six bins per axis (charge, electronegativity, H-bond donor, two types of polarizability, molecular surface area) derived using DiverseSolutions. 

Figure 8. Chemistry space occupation for reference databases, using a 6 dimensional BCUT chemistry space derived using DiverseSolutions and 6 bins per axis.

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