Comparative molecular similarity CoMSIA

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

CoMSIA Comparative molecular similarity index analysis... 

CoMSIA comparative molecular similarity indices analysis... 

CoMFA comparative molecular field analysis, CoMSIA comparative molecular similarity indices analysis... 

A similarity measure between two molecules s and t in any relative orientation to each other, used in CoMSIA (-> comparative molecular similarity analysis) and defined as [Kearsley and Smith, 1990] ... 

CoMSIA Comparative Molecular Similarity Indices Analysis... 

CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) not only derive a mathematical equation but also generate a contour map (e.g., steric or electrostatic fields) that should or should not be occupied by new compounds with optimized characteristics (Fig. 34.6). 

Statistical characteristics of CMF models obtained for these data sets were compared with the same characteristics built for corresponding data sets using the common 3D-QSAR methods, CoMFA (Comparative Molecular Fields Analysis) [18] and CoMSIA (Comparative Molecular Similarity Index Analysis) [24], based on the use of molecular fields. Data on CoMFA and CoMSIA models were taken from Ref. [25]. 

Klebe, G. (1998). Comparative Molecular Similarity Indices CoMSIA In 3D QSAR in Drug Design.., H. Kubinyi, G. Folkers, and Y.C. Martin (eds). Kluwer Academic Publishers, London, UK. 3 87. 

Bringmann G, Rummey C (2003) 3D QSAR investigations on antimalarial naphthylisoqui-noline alkaloids by comparative molecular similarity indices analysis (CoMSIA), based on different alignment approaches. J Chem Inf Comput Sci 43(1) 304-316... 

Klebe, G. and Abraham, U. (1999). Comparative Molecular Similarity Index Analysis (CoMSIA) to Study Hydrogen-Bonding lYoperties and to Score Combinatorial Libraries. J.ComputAid. Molec.Des., 13,1-10. 

Labrie, P., Maddaford, S.P.. Fortin, S., Rakhit, S., Kotra, L.P., and Gaudreault, R.C. (2006) A comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of anfhranilamide derivatives fhat are multidrug resistance modulators. Journal of Medicinal Chemistry, 49 (26), 7646-7660. 

Doytchinova, LA. and Flower, D.R. (2002) A comparative molecular similarity index analysis (CoMSIA) study identifies an HLA-A2 binding supermotif./. Comput. Aid. Mol. Des., 16,535—544. 

Still based on molecular interaction fields, several other methods were successively proposed and, among them, there were Comparative Molecular Similarity Indices Analysis (CoMSIA) ]Klebe, Abraham et al, 1994], Compass method ]Jain, Koile et al, 1994], G-WHIM descriptors ]Todeschini, Moro et al, 1997], Voronoi field analysis [Chuman, Karasawa et al, 1998], VolSurf descriptors ]Crudani, Pastor et al, 2000], and GRIND descriptors ]Pastor, Cruciani et al, 2000]. 

A variety of QSAR models have also been investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) [91, 92] models have been used for the substrate-based and keto acid inhibitors (represented by compounds 27 and 30). Molecular overlays were initially developed for each class, and by comparison of activity data with these overlays, a model can be developed to take into account both steric and electrostatic fields around the inhibitors this is illustrated in Fig. 5 [91]. 

Klebe G (1998) Comparative molecular similarity indices, CoMSIA. In Kubinyi H, Folkers G, Martin YC (eds) 3D QSAR in drug design. Kluwer Academic Publishers, Great Britain... 

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