Calculated molecular descriptor

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

G., Folkers, G., Raevsky, 0. A. Estimation of Gaco-2 cell permeability using calculated molecular descriptors. Quant. Struct.-Act. Relat. 1996, 15, 480 90. 

Numerous other QSAR models relating BBB penetration to calculated molecular descriptors have also appeared in literature see for example [27-29]. In each case, PSA was identified as one of the most important parameters determining blood-brain barrier penetration. 

Calculated molecular descriptors including H-bond parameters were used for QSAR studies on different types of permeabiUty. For example, the new H-bond descriptor characterizing the total H-bond ability of a compound, was successfully appUed to model Caco-2 cell permeability of 17 drugs [30]. A similar study on human jejunal in vivo permeabiUty of 22 structurally diverse compounds is described in Ref. [62]. An exceUent one-parameter correlation of human red ceU basal permeabiUty (BP) was obtained using the H-bond donor strength [63] ... 

Eros, D., Kovesdi, L, Orfi, L., Takacs-Novak, K., Acsady, G., Keril, G. Reliability of log P predictions based on calculated molecular descriptors a critical review. Curr. Med. Chem. 2002, 9,1819-1829. 

A common feature of the various methods that we have developed for the calculation of electronic effects in organic molecules is that they start from fundamental atomic data such as atomic ionization potentials and electron affinities, or atomic polarizability parameters. These atomic data are combined according to specific physical models, to calculate molecular descriptors which take account of the network of bonds. In other words, the constitution of a molecule (the topology) determines the way the procedures (algorithms) walk through the molecule. Again, as previously mentioned, the calculations are performed on the entire molecule. 

Three classes of calculated molecular descriptors, viz., topological and substruc-tural descriptors, geometrical (3-D) indices, and quantum chemical (QC) indices, have been extensively used in QSAR studies pertaining to drug discovery and environmental toxicology [8-12],... 

Symbols, Definitions and Classification of Calculated Molecular Descriptors... 

Pollutants with high VP tend to concentrate more in the vapor phase as compared to soil or water. Therefore, VP is a key physicochemical property essential for the assessment of chemical distribution in the environment. This property is also used in the design of various chemical engineering processes [49]. Additionally, VP can be used for the estimation of other important physicochemical properties. For example, one can calculate Henry s law constant, soil sorption coefficient, and partition coefficient from VP and aqueous solubility. We were therefore interested to model this important physicochemical property using quantitative structure-property relationships (QSPRs) based on calculated molecular descriptors [27]. 

Basak, S. C., Natarajan, R., Mills, D. Structure-activity relationships for mosquito repellent aminoamides using the hierarchical QSAR method based on calculated molecular descriptors, 2005, pp. 958-963. 

Predicted log BB with calculated molecular descriptors and concluded that BBB permeability can be increased by reducing the hydrogen-bonding ability of a compound. 

We have derived three sets of (easily calculated) molecular descriptors based on atomic contributions to logP, molar refractivity, and atomic partial charge. The individual descriptors were found to be weakly correlated with each other... 

The authors wish to thank Chris Gotts for collecting the sensory data Peter Bladon for assistance in calculating molecular descriptors. 

Three different variables are used for calculating molecular descriptors indicator variable, count variable, and graph-theoretical indices, as described below. Molecular... 

Because of convention, the symbols for the chemical potential, used in Equation 6.44 and Equation 6.45, and the dipole moment are the same. Further evaluation of Equation 6.48 proceeds through introduction of the LCAO-MO expansion (Equation 6.18) and, dependent on the level of theory, consideration of relevant approximations such as the NDDO formalism (Equation 6.31) in the case of semiempirical MNDO-type methods. Because the calculation of the dipole moment is usually considered a somewhat demanding test of the quality of the wavefunctions employed in the quantum chemical model, this property is included in the comparative statistical analysis of various methods to calculate molecular descriptors as presented in Section V. 

Charged molecules were neutralized with acidic and basic groups by adding or removing protons. This prevents the generation of structural differences caused by different protonation states, which might lead to differences in calculated molecular descriptors. 

Empirical, semiempirical, and ab initio methods have been used extensively to calculate molecular descriptors. These molecular property descriptors help capture important characteristics of compounds such as bioavailability and receptor affinity. Descriptors such as octanol-water partition coefficient (log P), HOMO/LUMO energies, hammett a, total energy, heats of formation, ionization potential, atomic charges, electron densities, dipole/quadrupole moments, volume, and polar surface area are common examples. For an excellent review of physicochemical descriptors, the reader is directed to the following reference. ... 

By calculating molecular descriptors based on 3D geometry without a common orientation frame, the Comparative Molecular Moment Analysis overcomes the problems due to the molecular alignment. 

Hemken, H.G. and Lehmann, P.A. (1992). The Use of Computerized Molecular Structure Scanning and Principal Component Analysis to Calculate Molecular Descriptors for QSAR. Quant.Struct-Act.Relat., 11,332-338. 

A disadvantage of the majority of these software is that they do not have the capability to calculate molecular descriptors. Thus additional software, such as DRAGON [71], Molconn-Z [72], or MODEL [73], are needed to enable toxicological QSAR models to be built. 

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