Drug similarity searches

While we were aware of the latent potential of COSMO-RS for drug similarity searches, it was a customer, Michael Thormann from MORPHOCHEM, who did the first similarity searches based on COSMO-RS a-profiles. He tried the simplest approach of -profile comparison. Applying a generalization of Tanimoto s binary similarity coefficient for real numbers to (7-profiles, the defined the similarity of two molecules X and X as... 

Following the similar structure - similar property principle", high-ranked structures in a similarity search are likely to have similar physicochemical and biological properties to those of the target structure. Accordingly, similarity searches play a pivotal role in database searches related to drug design. Some frequently used distance and similarity measures are illustrated in Section 8.2.1. 

Sheridan RP, Kearsley SK. Why do we need so many chemical similarity search methods Drug Discov Today 2002 7 903-11. 

Similarity Search and Structure-Based Drug Design... 

One early step in the workflow of the medicinal chemist is to computationally search for similar compounds to known actives that are either available in internal inventory or commercially available somewhere in the world, that is, to perform similarity and substructure searches on the worldwide databases of available compounds. It is in the interest of all drug discovery programs to develop a formal process to search for such compounds and place them into the bioassays for both lead generation and analog-based lead optimization. To this end, various similarity search algorithms (both 2D and 3D) should be implemented and delivered directly to the medicinal chemist. These algorithms often prove complementary to each other in terms of the chemical diversity of the resulted compounds [8]. 

The E-state indices may define chemical spaces that are relevant in similarity/ diversity search in chemical databases. This similarity search is based on atom-type E-state indices computed for the query molecule [55]. Each E-state index is converted to a z score, Z =(% -p )/0 , where is the ith E-state atomic index, p is its mean and O is its standard deviation in the entire database. The similarity was computed with the EucHdean distance and with the cosine index and the database used was the Pomona MedChem database, which contains 21000 chemicals. Tests performed for the antiinflamatory drug prednisone and the antimalarial dmg mefloquine as query molecules demonstrated that the chemicals space defined by E-state indices is efficient in identifying similar compounds from drug and drug-tike databases. 

Sheridan RP, Kearsley SK. (2002) Why Do We Need So Many Chemical Similarity Search Methods Drug Discov. Today 7 903-911. 

Muchmore, S. W., Souers, A. J., Akritopoulou-Zanze, I. (2006) The use of three-dimensional shape and electrostatic similarity searching in the identification of a melanin-concentrating hormone receptor 1 antagonist. Chem Biol Drug Des 67, 174-176. 

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