Electrostatic similarity searching

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. 

Thorner, D.A., Willett, P., Weight, P.M., and Taylor, R. Similarity searching in files of three-dimensional chemical structures Representation and searching of molecular electrostatic potentials using field-graphs./. Comput.-Aided Mol. Des. 1997, 3 3, 163-174. 

Wild, D.J. and Willett, P. Similarity Searching in Files ofThree-Dimensional Chemical Structures Alignment of Molecular Electrostatic Potentials with a Genetic Algorithm. J. Chem. Inf. Comput. Sci., 1996,36, 159-167. 

Similarity search conducts systematic search of functional site databases for chemical groups able to make ion pairs/hydrogen bonds and/or hydrophobic interactions with ligands from which representative sites as surfaces with electrostatic and hydrophobic characteristics are generated (Schmitt et al, 2002). 

D. A. Thorneg P. Willett, P. M. Wright, and R. Taylor, J. Comput.-Aided Mol. Des., 11,163 (1997). Similarity Searching in Files of Three-Dimensional Chemical Structures Representation and Searching of Molecular Electrostatic Potentials Using Field-Graphs. 

The product-moment correlation coefficient is widely used in bmriate data analysis to measure the extent of the correlation between two variables, but it is not clear that it is necessarily appropriate to measure the extent of the similarity between two objects. Other sorts of correlation coefficient are available, such as the Spearman rank correlation coefficient which has been used by Manaut et al. as a measure of electrostatic similarity, but these have not found extensive application in similarity searching systems. Similar comments apply to probabilistic coefficients, which are calculated from the frequency distribution of descriptors in a database, and which Adamson and Bush < found to give poor results when applied to 2D chemical structures. 

The description above has assumed that the property that is stored at the vertices of the tessellated icosahedron describing a molecule is either the minimal or the radial distance to the molecular surface. However, it is equally possible to store at each vertex any sort of property that can be calculated for that point in 3D space, such as the molecular electrostatic potential. Thus SPERM, like atom-mapping, allows local, property-based 3D similarity searching. 

Hodgkin EE, Richards WG (1987) Molecular similarity based on electrostatic potential and electric field. Int J Quantum Chem Quantum boil Symp 14 105-110 Sheridan RP, Kearsely SK (2002) Why do we need so many chemical similarity search methods Drug Discov Today 7 903-911... 

CAS has developed a molecular property similarity search capability that will allow the rapid scanning of millions of substances with good precision. The technique can be combined with other techniques such as topological similarity searching to provide more of a structure focus or it can act as a screening step for a subsequent, more computationally intensive technique to accomplish, for example, electrostatic similarity. 

Figure 3 Serotoninergic neare.st neighbors retrieved in a similarity search using electrostatic, steric, and hydrophobic fields...

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