BCUT descriptors, molecular similarity

Finally, there is one particular topological descriptor that should be mentioned because it has found considerable utility in a number of studies. This property, originally called a chemically intuitive molecular index by its inventor, Frank Burden, is based on a modified molecular adjacency matrix. The approach was extended by Pearlman " to take account of atomic charge, polarisability and hydrogen bonding ability, properties which are termed BCUT descriptors. BCUTs are available in a number of software packages and in addition to their utility in QSAR modelling, they have been shown to be useful measures of chemical similarity. 

An alternative to fingerprint based similarities are those based on BCUTs (Burden, CAS, University of Texas). This method uses a modified connectivity matrix (the Burden matrix) onto which are mapped atomic descriptors (such as atomic mass and polarizability) and connectivity information. The eigenvectors of this matrix represent a compressed summary of the information in the matrix and are used to describe a molecule. Typically 5-6 BCUT descriptors suffice to describe the chemical space of a set of molecules, and the space is usually partitioned into distinct bins , with each molecule assigned to the appropriate partition. In this format, similarity calculations become very simple molecules which are mapped into the same partition are similar. As an alternative, one could use larger numbers of molecular properties and a correlation vector approach. 

In our study we compare two diversity-driven design methods (uniform cell coverage and clustering), two analysis methods motivated by similarity (cell-based analysis and cluster-classification), and two descriptor sets (BCUT and constitutional). Thus, our study addresses some of the many questions arising in a sequential screen how to choose the initial screen, how to analyze the structure-activity data, and what molecular descriptor set to use. The study is limited to one assay and thus cannot be definitive, but it at least provides preliminary insights and reveals some trends. 

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... 

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