CAESAR II:The Combination of Direct Geometry Method and CAESAR Algorithm for Super Fast Conformational Search
by Accelrys on Apr 26, 2010
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A new method called Direct Geometry, is proposed for 3D structure generation of molecules with various types of geometric constraints such as ring closures, chirality and cis-trans isomerism. This ...
A new method called Direct Geometry, is proposed for 3D structure generation of molecules with various types of geometric constraints such as ring closures, chirality and cis-trans isomerism. This method is combined with the original CAESAR algorithm for super-fast conformation searches. The new method is based on a very simple iterative procedure which directly modifies atom coordinates according to the geometric constraints, such as bond lengths, bond angles, torsions, and various stereochemical constraints. As compared to the traditional Distance Geometry method, the new method is much simpler and more efficient for highly constrained molecules. The techniques for stabilizing and accelerating convergence are presented. The efficiency and the robustness of the Direct Geometry method are demonstrated by the successful 3D structure generation of C60 and other highly constraint structures from completely random coordinates. To further improve the overall performance, a new ring library technology is designed for better re-use and fast retrieval of ring conformations. Our test with nearly 6 million compounds shows that the new integrated method, called CAESAR II, the 2nd generation of the CAESAR algorithm, is significantly faster than the original one. The high performance suggests that the new algorithm can be used for on-the-fly conformation generation for many applications which involve conformational models. Validation studies, such as conformation diversity measurements, pharmacophore space coverage and the ability to reproduce of the bioactive conformation of ligands extracted from the Protein Data Bank (PDB) will be reported.
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