Drug design CoMFA applications

There are now a few hundred practical applications of CoMFA in drug design. Most applications are in the field of ligand-protein interactions, describing affinity or inhibition constants. In addition, CoMFA has been used to correlate steric and electronic parameters.Less appropriate seems the application of CoMFA to in vivo data, even if lipophilicity is considered as an additional parameter. As most CoMFA applications in drug design have been comprehensively reviewed in three books and in some reviews, " Table 1 gives only an overview of some typical applications that have been reported in the last few years. 

Folkers, G., Merz, A., Rognan, D. CoMFA Scope and Limitations. In 3D QSAR in Drug Design. Theory, Methods and Applications, Kubinyi, H. (ed.), ESCOM Science Publishers, Leiden, 1993. 

Beside the descriptors, further attempts have been made to encode the 3D molecular structures with functions. Such are 3D-MoRSE code [54] spectrum-like representations [55] and radial distribution functions [56]. Also, experimentally determined infrared, mass, or NMR spectra can be taken to represent a molecule [57]. Another example is comparative molecular field analysis (CoMFA) where the molecular 3D structures are optimized together with the receptor [58]. This approach is often applied in drug design or in specific toxicology studies where the receptor is known. The field of molecular descriptors and molecular representations has exploded in the recent decades. Over 200 programs for calculating descriptors and different QSAR applications are listed on web page [59]. 

Martin, Y.C., Lin, C.T. and Wu, J. (1993) Appbcation of CoMFA to D1 dopaminergic agonists a case study, in 3D QSAR in Drug Design. Theory, Methods and Applications (ed. H. Kubinyi), ESCOM, Leiden, The Netherlands, pp. 643-659. 

Kim KH, Greco G, Novellino E. A critical review of recent CoMFA applications. In Kubinyi H, Folkers G, Martin YC, eds. 3D QSAR in Drug Design. Vol. 3. Recent Advances. Dordrecht Kluwer/ESCOM, 1998 257-315. 

Van de Waterbeemd, H., Qementi, S., Costantino, G., Carrupt, P.-A., Testa, B. CoMFA derived substituent descriptors for structure-property correlations. In 3D QSAR in drug design theory, methods, and applications (Kubinyi, H., Ed.). ESCOM Leiden, 1993, pp. 697-707. 

Martin YC, Lin CT, Wu J (1993) Application of CoMFA to D1 dopaminergic agonists A case study. In Kubinyi H (ed) 3D QSAR in drug design theory methods and applications. ESCOM, Leiden, p 643... 

G. Folkers, A. Merz, and D. Rognan, in 3D-QSAR in Drug Design Theory Methock and Applications, H. Kubinyi, Ed., ESCOM, Leiden, 1993, pp. 583-618. CoMFA Scope and Limitations. See also references within. 

U. Thibaut, G. Folkers, G. Klebe, H. Kubinyi, A. Merz, and D. Rognan, in 3D-QSAR in Drug Design Theory Methods and Applications, H. Kubinyi, Ed., ESCOM, Leiden, 1993, pp. 711-716. Recommendations for CoMFA Studies and 3D QSAR Publications. Y. C. Martin, K.-H. Kim, and C. T. Lin, in Advances in Quantitative Structure-Property Relationships, M. Charton, Ed., JAl Press, Greenwich, CT, 1996, Vol. 1, pp. 1—52. Comparative Molecular Field Analysis CoMFA. 

Table 1 Overview on some Typical CoMFA Applications in Drug Design. Abstracted in the years i993-i996...

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