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2D-3D MIGRATION AND CONFORMATIONAL MULTIPLICATION OF CHEMICALS IN LARGE CHEMICAL INVENTORIES
Citation:
Grancharov, V., S. Dimitrov, V. Kamenska, G. Stoyanova, P. K. Schmieder, AND O. G. Mekenyan. 2D-3D MIGRATION AND CONFORMATIONAL MULTIPLICATION OF CHEMICALS IN LARGE CHEMICAL INVENTORIES. Presented at SETAC Europe Annual Meeting, Prague, Czech Republic, April 4, 2004.
Description:
Chemical interactions are three-dimensional (3D) in nature and require modeling chemicals as 3D entities. In turn, using 3D models of chemicals leads to the realization that a single 2D structure can have hundreds of different conformations, and the electronic properties of these conformations can vary substantially. Conformational flexibility appears to be a significant structural feature expecially when receptor-mediated toxic endpoints are modelled. A new approach based on a genetic algorithm was used to provide coverage of the conformational space with a limited number of conformers. Unique conformers are generated by exploring the following stereochemical and conformational degrees of freedom: rotation around acyclic single and double bonds, inversion of stereocenters, flip of free corners in saturated rings, reflection of pyramids on the junction of two or three saturated rings, reflection of pyramids on the junction of two or three saturated rings. Optimization is achieved by minimizing 3D similarity among the generated conformers. The fitness function was based on the combination of the root-mean-square distance between conformers and Shannon entropy formula. The approach is especially effective for highly flexible chemicals. Its conformational multiplication of chemicals is described along with the performance of the system for building large 3D chemical inventories.