Descriptors alignment-free

Borosy, A.P., Balogh, B. and Matyus, P. (2005) Alignment-free descriptors for quantitative structure-rate constant relationships of [4 + 2] cycloadditions./. Mol, Struct. (Theochem), 729, 169-176. 

Further additions to the 3D-QSAR arsenal include comparative molecular similarity indices analysis (CoMSIA) [15], 4D-QSAR [16], COMPASS [17], receptor surface models [18], the pseudoreceptor approach [19], ComPharm [20], and comparative molecular surface analysis (CoMSA) [21], 3-D-invariant, alignment-free descriptor systems such as comparative molecular moment analysis (CoMMA) [22], EVA [23], WHIM [24], and ALMOND [25], have also become available. A survey of the 3D-QSAR literature reveals 1154 entries in the Chemical Abstracts Plus database of these, 79% are journal publications, 19% are conference proceedings, and four are patents related to, or using, 3D-QSAR models. As the number of potential targets amenable to drug discovery is increasing exponentially, it is likely that 3D-QSAR models and methodologies will continue to be developed in the next decade. 

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 basic idea of alignment-free shape matching is that a set of rotation- and translation-free descriptors are calculated for con-formers under consideration, and then some similarity measure is devised to quantify the similarity between two molecular objects. Zauhar s shape signatures (45), Breneman s PEST and PESD methods (54-56), the USR (ultrafast shape recognition) method... 

The molecular interaction fields (MIF) obtainable by GRID [1] may be used to define the solvent accessible surface, which resembles the molecular shape. However, MIFs are descriptors that depend on the 3D-location, and usually several thousand are required to describe a shape. In this chapter we present a novel procedure, called PathFinder, which encodes MIF into a compact alignment-free description of molecular shape. 

F. Fontaine, M. Pastor, H. Gutierrez de Teran, J. J. Lozano, F. Sanz, Use of alignment-free molecular descriptors in diversity analysis and optimal sampling of molecular libraries. Mol. Diversity 2003, 6 (2), 135-147. 

E. Eontaine, M. Pastor, E. Sanz, Incorporating molecular shape into the alignment-free GRid-INdependent Descriptors, J. Med. Chem. 2004, 47 (11), 2805-2815. 

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