Numerous theoretical methods in the field of computational chemistry falls back on the availability of 3D structural information about compounds. Determining molecular structure without human interaction is an essential component of several techniques, like QSAR, 3D pharmacophore analysis, reaction prediction, etc. Current computational tools used for structure determination including force-fields and quantum chemical methods, even require a complete set of initial 3D coordinates. The efficiency of 3D structure based HTS tools also can be enhanced by employing conformational analysis to yield multiple valid structures.

Our approach utilize a composition of several methods ranging from pure rule based (as classified in [3]) multi dimensional distance geometry method (described in [1]) to data based stored substructure lookup features in a flexible software framework. The actual implementation is a highly portable JAVA software, which fits a broad scale of applications: it is used in small web drawing applets (available at [2]) as well as standalone database processing component. The coordinate/conformer generation process uses the Dreiding force field for energy calculations. Geometry structure optimization and molecular dynamics calculations are also implemented.

The coordinate determination process can be best characterized by the “divide and conquer” approach: the structure is composed of fragments, which are joined together. From the available fragment conformers the conformers of the joined structures can be generated during the fusing step. The fragment conformers are generated either through further fragmentation or with an elemental structure/conformer prediction method, consequently the conformational analysis is an inherent part of the building process (in contrast with methods proceeds from 3D initial structures like [4]). The novelty of our approach lies in the diversity of utilized such elemental methods and the arisen scalability options.

References [1] G. Imre, G. Veress, A. Volford and Ö. Farkas, ”Molecules from the Minkowski Space: An approach to building 3D molecular structures”, J. Mol. Struct. (Theochem), 666-667, 51-59 (2003) [2] /marvin [3] J. Sadowski and J. Gasteiger, “From Atoms and Bonds to Three-Dimensional Atomic Coordinates: Automatic Model Builders”, Chem. Rev., 93, 2567-2581 (1993) [4] J. Weiser, M. C. Holthausen, L. Fitjer, .HUNTER: “A Conformational Search Program for Acyclic to Polycyclic Molecules with Special Emphasis on Stereochemistry”, J. Comput. Chem., 18, 1265-1281 (1997)