Molecular Moment Analysis CoMMA

The reader will appreciate that the problem of molecular superposition is a difficulty with many 3D-QSAR methods. The comparative molecular moment analysis (CoMMA) method overcomes this obstacle by calculating descriptors based on the 3D structures without reference to a common orientation frame.  

CoMMA uses 13 descriptors of shape and electrostatic properties. The pure shape descriptors are the three principal moments of inertia, and the two pure electrostatic descriptors are the magnitude of the dipole moment and the magnitude of the principal quadrupole moment. To complement these, six additional descriptors that relate shape and charge are calculated the dipolar components as well as the magnitudes of the components of displacement between the center of mass and the center of dipole along the three principal axes of inertia. Last, quadrupolar components are calculated with respect to a translated initial reference frame whose origin coincides with the center of dipole. 

3D-QSAR METHODS THAT REC RE 3D STRUCTURES OF THE LIGAND-MACROMOLECULE COMPLEXES 

If the 3D structure of the complex is known, a variety of methods can be used to forecast the affinity of new compounds. - However, these de novo potency predictions suffer from inaccuracies that can be sidestepped if the unknown compound is similar in structure to a known substance. We restrict 

Several groups have applied CoMFA to series in which the 3D structures of at least some of the complexes are Usually the 

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Silverman, B. D. and Platt, D. E. (1996) Comparative molecular moment analysis (CoMMA) 3D-QSAR without molecular superposition. J. Med. Chem. 39, 2129-2140. 

Silverman, B.D., Platt, D.E., Pitman, M. and Rigoutsos, I. (1998b). Comparative Molecular Moment Analysis (CoMMA). In 3D QSAR in Drug Design - Vol. 3 (Kubinyi, H., Folkers, G. and Martin, Y.C., eds.), Kluwer/ESCQM, Dordrecht (The Netherlands), pp. 183-198. 

Silverman, B.D. (2000a) The thirty-one benchmark steroids revisited comparative molecular moment analysis (CoMMA) with principal component regression. Quant. Struct. -Act. Relat., 19, 237-246. 

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. 

Silverman DB, Platt DE, Pitman M, Rigoutsos I. Comparative molecular moment analysis (CoMMA). In Kubinyi H, Folkers G, Martin YC, eds. 3D QSAR in Drug Design. Vol. 3. Recent Advances. Dordrecht Kluwer/ESCOM, 1998 183-196. 

Silverman BD, Platt DE (1996) Comparative molecular moment analysis (CoMMA) 3D-... 

B. D. Silverman and D. E. Platt,/. Med. Chem., 39, 2129 (1996). Comparative Molecular Moment Analysis (CoMMA)—3D-QSAR Without Molecular Superposition. 

Comma descriptors comparative molecular moment analysis... 

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