Comparative molecular similarity indices

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... 

The next step was made by Klebe et al. [50]. Two 3D-QSAR methods were applied to get three-dimensional quantitative structure-activity relationships using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities toward Factor Xa to yield statistically reliable models of good predictive power [51-54] the widely used CoMFA method (for steric and electrostatic properties) and the comparative molecular similarity index analysis (CoMSlA) method (for steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties). These methods allowed the consideration of various physicochemical properties, and the resulting contribution maps could be intuitively interpreted. 

CoMSlA Comparative molecular similarity indexes analysis... 

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. 

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. 

CoMSIA Comparative Molecular Similarity Index Analysis... 

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, Abraham U (1999) Comparative molecular similarity index analysis (CoMSIA) to study hydrogen-bonding properties and to score combinatorial libraries. J Comput-Aided Mol Des 13(1) 1-10... 

The pragmatic beauty of the chemical fingerprint is that the more common features of two molecules that there are, the more common bits are set. The mathematic approach used to translate the fingerprint comparison data into a measure of similarity tunes the molecular comparison [5]. The Tanimoto similarity index works well when a relatively sparse fingerprint is used and when the molecules to be compared are broadly comparable in size and complexity [5]. If the nature of the molecules or the comparison desired is not adequately met by the Tanimoto index, multiple other indices are available to the researcher. For example, the Daylight software offers the user over ten similarity metrics, and the Pipeline Pilot as distributed offers at least three. Some of these metrics (e.g., Tversky, Cosine) offer better behavior if the query molecule is significantly smaller than the molecule compared to it. 

Using the Carbo index, molecular similarity C b determined from the structural properties P and Pg of molecules A and fi compared over all space. The numerator measures property overlap, while die denominator normalizes the similarity result. Many alternative formalisms have been proposed for the calculation of molecular similarity between two overlaid molecules. - ... 

The A-MSD intercorrelation coefficient is rather low, r=-0.65. This may be partly due to the fact that A used for QSAR by Amoore et al. is a similarity index. A=1/(1+A ), where A is directly related to the shape differences of molecular contours and thus A should be compared to MSD. 

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