Contour� is a structure-based drug design technology that comprises a context perceptive growth algorithm and a contact sensitive scoring function.  A flexible and programmable growth engine creates drug-like molecules by assembling fragments in the context of protein binding pockets. The context sensitive algorithm is designed to generate novel molecules that naturally complement hydrophilic and hydrophobic features of the protein binding site through its dynamic growth features. At each stage of the growth process the local binding site features are dynamically mapped, and these features pick high ranking fragments and attach them in the best direction(s) to grow. Once the fragments are assembled in the binding site, growth algorithm scans fragment atoms that are in contact with the protein atoms in the binding site and dynamically mutates select atoms into complementary hetero atoms. Thus these features generate molecules that best complement the shape and the features of protein binding sites. These improvements have significantly enhanced the growth rate up to 10 times over the previous version of the growth algorithm, and raised the average score of molecules generated by about 1 log unit. We demonstrate these features with application to renin, 11� HSD-1, and LXR.

Contour<sup>�</sup> growth algorithm builds novel drug-like molecules in the context of protein binding site

248th National Meeting (2014)

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Contour� growth algorithm builds novel drug-like molecules in the context of protein binding site

Contour^� growth algorithm builds novel drug-like molecules in the context of protein binding site