Continuous indicator fields: a novel universal type of molecular fields.

Sitnikov, Gleb; Zhokhova, Nelly; Ustynyuk, Yury; Varnek, Alexandre; Baskin, Igor

A novel type of molecular fields, Continuous Indicator Fields (CIFs), is suggested to provide 3D structural description of molecules. The values of CIFs are calculated as the degree to which a point with given 3D coordinates belongs to an atom of a certain type. They can be used similarly to standard physicochemical fields for building 3D structure-activity models. One can build CIF-based 3D structure-activity models in the framework of the continuous molecular fields approach described earlier (J Comput-Aided Mol Des 27 (5):427-442, ) for the case of physicochemical molecular fields. CIFs are thought to complement and further extend traditional physicochemical fields. The models built with CIFs can be interpreted in terms of preferable and undesirable positions of certain types of atoms in space. This helps to understand which changes in chemical structure should be made in order to design a compound possessing desirable properties. We have demonstrated that CIFs can be considered as 3D analogues of 2D topological molecular fragments. The performance of this approach is demonstrated in structure-activity studies of thrombin inhibitors, multidentate N-heterocyclic ligands for Am/Eu separation, and coloring dyes.

QSAR models; KERNEL functions; RIDGE regression (Statistics); COMPLEXATION reactions; METAL complexes; CHEMICAL structure

Journal of Computer-Aided Molecular Design, 2015, Vol 29, Issue 3, p233

0920-654X

Academic Journal

10.1007/s10822-014-9818-z