Descriptor flexible

FHDSA index RSHM index -> charged partial surface area descriptors flexibility index based on path length - flexibility indices flexibility indices... 

The terms similarity and diversity can have quite different meanings in chemical investigations. Describing the diversity of a data collection with a general valid measure is almost impossible. Descriptor flexibility allows the characterization of similarity by means of statistics for different tasks. The statistical evaluation of descriptors shows that it is recommended to interpret correlation coefficients together with the symmetry of distribution. In contrast to correlation coefficients, skewness and kurtosis are sensitive indicators to constitutional and conformational changes in a molecule. This feature allows a more precise evaluation of structural similarity or diversity of molecular data sets. 

Further prerequisites depend on the chemical problem to be solved. Some chemical effects have an undesired influence on the structure descriptor if the experimental data to be processed do not account for them. A typical example is the conformational flexibility of a molecule, which has a profound influence on a 3D descriptor based on Cartesian coordinates. In particular, for the application of structure descriptors with structure-spectrum correlation problems in... 

In general, the described techniques provide an effective, flexible, and relatively fast solution for library design based on analysis of bioscreening data. The quantitative relationships, based on the assessment of contribution values of various molecular descriptors, not only permit the estimation of potential biological activity of candidate compounds before synthesis but also provide information concerning the modification of the structural features necessary for this activity. Usually these techniques are applied in the form of computational filters for constraining the size of virtual combinatorial libraries and... 

Duchowicz PR, Castro EA, Toropov AA, Benfenati E (2006) Applications of Flexible Molecular Descriptors in the QSPR-QSAR Study of Heterocyclic Drugs. 3 1-38... 

Taken globally, the results show a remarkable adaptability of acetylcholine which can be justified considering both its intrinsic flexibility, and the fact that its intramolecular interactions are not very strong and that almost all media can compete with them. Such adaptability finds a noteworthy implication in significant pairwise correlations between physicochemical properties and geometrical descriptors as well as among physicochemical properties. Thus, Fig. 1.6 shows the revealing 3D... 

This also involves flexibility and rigidity descriptors (RB and AP), a size descriptor (MW) and a polarity descriptor (log Pow). It appears that these kinds of descriptors are essential for AGfUs-... 

Flexible optimal descriptors have been defined as specific modifications of adjacency matrix, by means of utilization of nonzero diagonal elements (Randic and Basak, 1999, 2001 Randic and Pompe, 2001a, b). These nonzero values of matrix elements change vertex degrees and consequently the values of molecular descriptors. As a rule, these modifications are aimed to change topological indices. The values of these diagonal elements must provide minimum standard error of estimation for predictive model (that is based on the flexible descriptor) of property/activity of interest. 

However, the CIMI/bc descriptors are relatively simplistic as they did not recognize differences between some important atom types (e.g., halogens). Based on the results of ARD approach, the octanol-water partition coefficient (log P), the molecular flexibility (number of rotatable bonds), the PSA, and the number of hydrogen bond donors were the most important descriptors in the model. None of the descriptors were significantly correlated with each other except log P and PSA for which the correlation was not high ( 0.5). The molecular weight was found to be the least significant descriptor in the model. 

Property-based descriptors, lipophilicity, molecular flexibility, PSA, and number of hydrogen-bond donors are the main parameters influencing the BBB permeability of compounds. 

WOMBAT [39] is a Cabinet database that provides information about biological activity of small molecules [40]. The dataset comes from publications in the Journal of Medicinal Chemistry and other periodicals. WOMBAT is updated twice a year. The data consist of series of compounds that were observed and compared for a specific activity, for example, Ki, IC50, D2 and EC50. The database also includes calculated LogP and Log S values, as well as other descriptors related to flexibility, size, and so on. 

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... 

METEOR S biotransformation rules are generic reaction descriptors, and the versatile structural representation used in the system allows each atom or bond to have specific physicochemical properties. This approach provides more details than simple hard-coded functional group descriptors (313), but this flexibility also can give rise to an avalanche of data. METEOR manages the amount of data by predicting which metabolites are to be formed rather than all the possible outcomes (310,312,314,315). At high certainty levels, when chosen, only the more likely biotransformations are requested. At lower likelihood levels, the more common metabolites are also selected for examination. Currently, METEOR knowledge-based biotransformations are exclusively for mammalian biotransformations (phase I and phase II) (314,315). 

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