3D molecular descriptor

The VolSurf approach was used to correlate the 3D molecular descriptors by utilizing the water solubilities for as many compounds as could be found. Although over 2000 solubility values were identified, many showed contradictory results (both low and high values published). Moreover, some of the estimations had not been made by the authors and the original reference was not reported, while others were simply wrong, having not been measured under the standard conditions required. From the 2000 compounds, about 850 were carefully selected in addi-... 

D-molecular descriptors, alignment-independent and based on molecular interaction, called GRIND have been developed. These are autocorrelation transforms that are independent of the orientation of the molecules in 3D space. The original descriptors can be extracted from the autocorrelation transform with the ALMOND program. The basic idea is to compress the information present in 3D maps into a few 2D numerical descriptors which are very simple to understand and interpret. 

Nettles, J.H., Jenkins, J.L., Bender, A., Deng, Z., Davies, J.W. and Click, M. (2006) Bridging chemical and biological space Target Pishing using 2D and 3D molecular descriptors. Journal of Medicinal Chemistry, 49 (23), 6802-6810. 

Aptula, A.O., Kiihne, R., Ebert, R.-U., Cronin, M.T.D., Netzeva, T.I., and Schuurmann G., Modeling discrimination between antibacterial and non-antibacterial activity based on 3D molecular descriptors, QSAR Combinatorial Sci., 22, 113-128, 2003. 

Todeschini, R. and Gramatica, P., The WHIM theory new 3D molecular descriptors for QSAR in environmental modelling, SAR QSAR Environ. Res., 7, 89-115, 1997a. 

In selecting molecular descriptors upon which to base a QSAR model, one needs to know the role that these parameters play, either the way the chemical behaves or the way the studied endpoint is expressed [4], While 3D molecular descriptors are now widely used in drug design [12], most QSAR models in environmental sciences are derived from 2D molecular descriptors that are broadly classified into three main types (Figure 23.2). 

Another drawback of 3D molecular descriptors worth consideration is that they are sensitive to the position and orientation of the molecular structures in space. Tropsha and Cho have demonstrated that the results of conventional CoMEA are sensitive to the overall orientation of superimposed molecules. They show that for a given alignment analyzed in different orientations, the single (f value obtained from standard CoMEA will most likely fall within the region of the highest frequency of q. Therefore, they propose cross-validated guided region selection for CoMEA... 

One way to 3D molecular descriptors is deriving them from molecular transforms, which are generalized scattering functions used to create theoretical scattering curves in electron diffraction studies. A molecular transform serves as the functional basis for deriving the relationship between a known molecular structure and x-ray and electron diffraction data. The general molecular transform is... 

D Molecular Descriptors are molecule representations based on Cartesian coordinates and Euclidean distances. 

Important kinds of matrices are the molecular matrix, which collects atom spatial coordinates, and all the matrices related to molecular geometry, such as the geometry matrix, whose 3D molecular descriptors are derived from, and computational chemistry approaches are based on, WHIM weighted covariances matrices and the molecular influence... 

Consonni, V., Todeschini, R. and Pavan, M. (2002a) Structure/response correlations and similarity/ diversity analysis by GETAWAY descriptors. Part 1. Theory of the novel 3D molecular descriptors. 

Kabankin, A.S. and Gabrielyan, L.l. (2005) Relationship between structure and hepatoprotector activity of adamantane derivatives. Part 2. Application of autocorrelative, substructural and 3D molecular descriptors. Pharm. Chem.f, 39, 135-139. 

Todeschini R, Gramatica P. New 3D molecular descriptors The WHIM theory and QSAR applications. In Kubinyi H, Folkers G, Martin YC, eds. 3D QSAR in Drug Design. Vol. 2. Ligand Protein Interactions and Molecular Similarity. Dordrecht Kluwer/ESCOM, 1998 355-380. 

The first four chapters and Chapter 6 are connected with 3D molecular descriptors and their uses for QSAR and molecular similarity studies associated with molecular modeling of agonist-receptor interactions, with drug design, and with the discovery of new lead compounds for various types of biological activities. 

Calculation of 3D molecular descriptors 3D QSAR, Molecular Conformation and Superposition... 

An important draw-back of all 3D molecular descriptors is that they are sensitive to the position and orientation of... 

Nicholls, A., MacCuish, N.E., and MacCuish, J.D. (2004) Variable selection and model validation of 2D and 3D molecular descriptors. Journal of Computer-Aided Molecular Design, 18, 451-474. 

Several new 2D and 3D molecular descriptors have been invented and proposed for QSAR use [4]. However, (he relatively high uncertainty associated with molecular descriptors constitutes a difficult problem. Thus, the search for more informative 2D and/or 3D molecular descriptors has been of major concern in QSAR research. Using variable selection from a very large pool of descriptors, PLS can detect the informative molecular descriptors [5]. 

---