Information content descriptors

It has often been mentioned in this chapter that many molecular descriptors can well be highly intcr-corrclatcd. Therefore, any significant information content of a... 

The information content of a structure descriptor depends on two major factors a) the molecular representation of the compound b) the algorithm which is used for the calculation of the descriptor. 

Two-dimensional H-bond descriptors are included in Table 6.1. Considering information content, they may be classified as indirect descriptors (no direct link with the H-bonding process), H-bond indicators (atoms having potential H-bond capability) and thermodynamic factors (calculated on the basis of experimental thermodynamic data of H-bonding). 

Another possible advantage with MolSurf descriptors (and also other multi parameter descriptors) is the fact that they describe the investigated compounds not only with a single value, as in the case of PSA and log P descriptors, but in a multivariate way. This approach provides a more balanced description of the requirements that a structure must have in order to be well absorbed and may, in turn, provide additional insight on how to develop compounds having favorable absorption properties. However, as will be described in Section 16.4.10, simpler -i.e., less computationally demanding - parameters carrying similar information content with equal interpretability may be used to derive models for intestinal absorption at the same level of statistical quality. 

Brown RD, Martin YC. (1997) The Information Content of 2D and 3D Structural Descriptors Relevant to Ligand-Receptor Binding. /. Chem. Inf. Comp. Sci. 37 1-9. 

The chapter is divided into three sections the first part is concerned with the derivation of 3D-LogP descriptor and the selection of suitable parameters for the computation of the MLP values. This study was performed on a set of rigid molecules in order, at least initially, to avoid the issue of conformation-dependence. In the second part, both the information content and conformational sensitivity of the 3D-LogP description was established using a set of flexible acetylated amino acids and dipeptides. This initial work was carried out using log P as the property to be estimated/predicted. However, it should be made clear that, while the 3D-LogP descriptor can be used for the prediction of log P, this was not the primary intention behind its the development. Rather, as previously indicated, the rationale for this work was the development of a conformationally sensitive but alignment-free lipophilicity descriptor for use in QSAR model development. The use of log P as the property to be estimated/predicted enables one to establish the extent of information loss, if any, in the process used to transform the results of MLP calculations into a descriptor suitable for use in QSAR analyses. 

The SlogP, SMR, and PEOE VSA descriptors have rich information content and can be used in place of many traditional descriptors (13-17). Figure 5 presents the results of a collection of 64 linear models each of which approximates a traditional descriptor as a linear combination of the VSA descriptors (trained on approx 2,000 small molecules). Out of the 64 descriptors, 32 showed an r2 of 0.90 or better and 49 had an r2 of 0.80 or better, and 61 showed an r2 of 0.5 or better. Descriptors related to flexibility are poorly modeled. In particular, the Lipinksi parameters log/5, acceptor count, donor count, and molecular weight are... 

Godden, J. W. and Bajorath, J. (2002) Chemical descriptors with distinct levels of information content and varying sensitivity to differences between selected compound databases identified by SE-DSE analysis. J. Chem. Inf. Comput. Sci. 42, 87-93. 

R.D. Brown, Y. C. Martin. The information content of 2D and 3D structural descriptors relevant to ligand-receptor binding. J. Chem. Inf. Comput. Sci., 37, 1-9, 1997. 

C2Descriptor+ Accelrys Inc. www.accelrys.com/cerius2/descriptor.html Topological indices, information content indices, fingerprint descriptors, physicochemical properties, charged partial surface area descriptors, shadow indices... 

Brown and Martin [57] also investigated the extent to which a number of different descriptors (2-D and 3-D) are able to encode information that relates to the interaction forces which must exist if a ligand is to bind to a receptor. Thus, the information content of each descriptor was assessed by its ability to accurately predict values for the physical properties of a structure from the... 

Apart from their application in practical problems, the GRIND have been the subject of some theoretical papers, dealing for instance [28] with their information content, performing comparisons with other descriptors and discussing their suitability in drug discovery. 

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