Descriptor calculation

Topological descriptors and 3D descriptors calculated in distance space", such as 3D autocorrelation, surface autocorrelation, and radial distribution function... 

The abbreviation QSAR stands for quantitative structure-activity relationships. QSPR means quantitative structure-property relationships. As the properties of an organic compound usually cannot be predicted directly from its molecular structure, an indirect approach Is used to overcome this problem. In the first step numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical methods and artificial neural network models are used to predict the property or activity of interest, based on these descriptors or a suitable subset. A typical QSAR/QSPR study comprises the following steps structure entry or start from an existing structure database), descriptor calculation, descriptor selection, model building, model validation. 

Building a QSPR model consists of three steps descriptor calculation, descriptor analysis and optimization, and establishment of a mathematical relationship between descriptors and property. 

The molecular mechanics force fields available include MM+, OPLS, BIO+, and AMBER. Parameters missing from the force field will be automatically estimated. The user has some control over cutoff distances for various terms in the energy expression. Solvent molecules can be included along with periodic boundary conditions. The molecular mechanics calculations tested ran without difficulties. Biomolecule computational abilities are aided by functions for superimposing molecules, conformation searching, and QSAR descriptor calculation. 

Two models of practical interest using quantum chemical parameters were developed by Clark et al. [26, 27]. Both studies were based on 1085 molecules and 36 descriptors calculated with the AMI method following structure optimization and electron density calculation. An initial set of descriptors was selected with a multiple linear regression model and further optimized by trial-and-error variation. The second study calculated a standard error of 0.56 for 1085 compounds and it also estimated the reliability of neural network prediction by analysis of the standard deviation error for an ensemble of 11 networks trained on different randomly selected subsets of the initial training set [27]. 

Korany et al. [28] used Fourier descriptors for the spectrophotometric identification of miconazole and 11 different benzenoid compounds. Fourier descriptor values computed from spectrophotometric measurements were used to compute a purity index. The Fourier descriptors calculated for a set of absorbencies are independent of concentration and is sensitive to the presence of interferents. Such condition was proven by calculating the Fourier descriptor for pure and degraded benzylpenicillin. Absorbance data were measured and recorded for miconazole and for all the 11 compounds. The calculated Fourier descriptor value for these compounds showed significant discrimination between them. Moreover, the reproducibility of the Fourier descriptors was tested by measurement over several successive days and the relative standard deviation obtained was less than 2%. 

We have carried out HiQSAR development using TS, TC, and 3-D descriptors, in addition to AMI semiempirical QC descriptors obtained using MOP AC 6.00 [52] and ab initio QC descriptors calculated with Gaussian 98W [66] using the STO-3G, 6-311G, and aug-cc-pVTZ basis sets, with results provided in Table 31.6. 

Toropov AA, Leszczynska D, Leszczynski J (2007a) QSPR study on solubility of fullerene C60 in organic solvents using optimal descriptors calculated with SMILES Chem. Phys. Lett. 441 119-122. 

The model has been claimed to predict the log BB values at a rate of 700 molecules per min, some two orders of magnitude faster than the calculations of Keserii and Molnar. To test the likely accuracy of such predictions, the authors took 105 compounds for which experimental descriptors were used in constructing equation (48) and calculated their log BB values using same with descriptors calculated by the method of Platts and workers. The observed and calculated values agreed with ESD = 0.294, thus indicating that Platts calculation method can be used in conjunction with equation (48) to predict further log BB values faster with an estimated accuracy of around 0.30 to 0.35 log units. 

When searching for possible descriptors for a traditional QSAR study, it is common practice to calculate all of the available descriptors, in some instances more than 300 descriptors including descriptors calculated from outside methods. 

This part of the case study was broken into two sections, the original descriptor set (2,125,127) (Hansch descriptors) and a new set of descriptors calculated in MOE (6) (MOE descriptors). The MOE Descriptors were calculated for molecules assigned Gasteiger (70) partial charges in the MMFF (46-52). The new descriptor set is constructed of three properties. The water accessible surface area (ASA) calculated using a radius of 1.4 A for a water molecule and the... 

Guha, 1C (2006) Chemistry Development Kit (CDK) descriptor calculator GUI (v 0.46). http //cheminfo.informatics. indiana.edu/rguha/code/java/cdkdesc.html (accessed October 2006). 

Fig. 3.2 Schematic of the CATS descriptor calculation, (a) The hydrogen-depleted two-dimensional molecular graph provides the input, (b) The graph is simplified for the distance matrix computation different bond orders are not considered (unweighted graph) and all element types are disregarded. The algorithm starts at an arbitrary chosen atom and visits all nodes of the graph in a breadth-first manner, thereby building up the distance matrix. The numbers at the vertices are used to reference individual atoms in the distance matrix.

In the following, we summarize the outcome of several studies that addressed further questions related to appropriate descriptor calculation. 

Figure 6.9 Descriptors calculated for phosphines in the irons-Rh (PR3)2(CO)CI catalyst a the deformation coordinate S4 is employed as steric measure b stereo-electronic map showingthe distribution of the various PR3 ligands.

Figure 6.15 Examples of topological descriptors calculated on backbone and R groups of three bidentate ligands. The broken arrows on the left indicate the minimum Pn-P2 connectivity path (Dt) and the second Pn-P2 path (D2). The dotted arrows indicate freely rotating bonds. The R group descriptor SAMR<3 pertains to the sum of the mass units of atoms that are connected within three bonds of the ligating P atoms.

The final step is incorporating the library generation, model selection, descriptor calculation, and catalyst screening in one workflow [66]. One way of doing... 

Martin et al. [68] have modeled together solubility of 14 polycyclic aromatic hydrocarbons (PAHs) and fullerene in octanol and heptane utilizing descriptors calculated with the CODESS A package [69]. Also in this case, the applicability domain has not been validated. The structural difference between planar PAHs and spherical fullerene is probably too large for making reliable predictions. Moreover, the experimental solubilities of fullerene in both solvents (log S = —4.09 in heptane and log S>4.18 in octanol) are significantly lower than the solubilities of PAHs (—3.80[Pg.211]

Product Name Provider Website Properties and Descriptors Calculated... 

Ensure the validity of a structure by using structural information without obvious errors in the structural description. Some structural errors are identified by chance, and others appear in the process of 2D to 3D structure conversion, geometry optimisation, and descriptor calculation. We pay specific attention... 

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