(139c) Improved Efficiency in the Ab Initio Generation of Crystal Structures

The CrystalPredictor^1,2 and CrystalOptimizer³ codes have been used to explore the space of crystal structures successfully in several crystal structure prediction (CSP) investigations in recent years, including in the series of blind tests organised by the Cambridge Crystallographic Data Centre⁴ and in the prediction of the crystal structures of pharmaceutically-relevant molecules^5-7. One of the key research challenges in developing CSP capabilities is to enable the investigation of increasingly flexible compounds within tractable computational times.

We present recent advances in CrystalPredictor that are focussed on addressing this challenge. Specifically, we discuss the smoothing of the intramolecular potential,⁸ an innovation in CrystalPredictor II that allows the most efficient use of computational effort to cover a flexible molecule’s conformational space. We also report the recent implementation of torsional grouping, a feature that retains the near quantum mechanical accuracy of the Local Approximate Model technique whilst greatly reducing the computational effort for compounds with more than 5 flexible torsions. These improvements achieve greater accuracy in the initial ranking of potential crystal structures, while managing computational cost, so that a thorough exploration of the search space is possible. We present CSP results for the NSAID drug Acemetacin to demonstrate this capability.

¹ M. Habgood, I. J. Sugden, A. V. Kazantsev, C. S. Adjiman, and C. C. Pantelides, J Chem Theory Comput 11, 1957 (2015).

² I. Sugden, C. S. Adjiman, and C. C. Pantelides, Acta Crystallogr B 72, 864 (2016).

³ A. V. Kazantsev, P. G. Karamertzanis, C. S. Adjiman, and C. C. Pantelides, J Chem Theory Comput 7, 1998 (2011).

⁴ A. M. Reilly, et al., Acta Crystallogr B 72, 439 (2016).

⁵ D. E. Braun, T. Gelbrich, K. Wurst, and U. J. Griesser, Cryst Growth Des 16, 3480 (2016).

⁶ D. E. Braun, V. Kahlenberg, and U. J. Griesser, Cryst Growth Des 17, 4347 (2017).

⁷ S. L. Price, D. E. Braun, and S. M. Reutzel-Edens, Chem Commun 52, 7065 (2016).

⁸ I. Sugden, C. S. Adjiman, and C. C. Pantelides, Acta Crystallogr B (In Preparation).