BCUT parameters

In addition to these fairly straightforward methods, several newer, more complex, analytical approaches have been developed. Among these are the multidimensional BCUT parameters developed by Pearlman or adaptations of the genetic algorithms and neural networks originally used for assessment of combinatorial library diversity. 

Vectors whose components have continuous values correspond to the more traditional types of vectors found in the physical sciences. They are of identical form to the discrete-valued vectors (see Eq. 2.16) except that the components, vA(xk), are continuous valued. In chemoinformatics, however, the nature of the components is considerably different from those typically found in physics. For example, physiochemical properties, such as logP, solubility, melting point, molecular volume, Hammett ap parameters, and surface charge, as well as other descriptors derived explicitly for the purpose, such as BCUTs... 

Samiulla et u/. report the design of natural product scaffolds that were then used in a small library of vasicinone derivatives. A key aspect of the design was the incorporation of parameters intended to result in improved ADME properties by including the filters proposed by Lipinski" and Veber et BCUTs were used to optimize the diversity of the scaffolds while Unity fingerprints were used in the diversity optimization of the vasicinone library. The measured solubility, permeability in MDCK cells and CYP inhibition were measured for the scaffolds. The resulting libraries demonstrated favorable distributions of each of the measured ADME properties. 

The BCUT descriptors are the lowest and highest eigenvalues of a connectivity matrix of a molecule in which the diagonal elements for each atom are assigned properties such as atomic charges, atomic polarizability, or atomic hydrogen bond parameters, respectively. 

An alternative to the use of principal components or factor analysis is the BCUT method of Pearlman [Pearlman and Smith 1998]. In this method, three square matrices are constructed for each molecule. Each matrix is of a size equal to the number of atoms in the molecule and has as its elements various atomic and interatomic parameters. One matrix is intended to represent atomic charge properties, another represents atomic polarisabilities and the third hydrogen-bonding capabilities. These quantities can be computed with semi-empirical... 

In a recent classification study, scaffolds taken from natural products were subjected to a two-step analysis in order to identify a diverse set of natural product scaffolds with preferred ADME-properties." Molecular diversity analysis and selection of natural product scaffolds were carried out using cell-based partitioning and the BCUT metrics." To approximate ADME parameters, rule-of-five " calculations were carried out. A set of about 50 natural product scaffolds fulfilled the desired diversity and ADME criteria. ... 

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