(136a) Accurate and Efficient Representation of Intramolecular Energy in Ab Initio Generation of Crystal Structures

The CrystalPredictor I^1,2 and II³ codes have been used to explore the space of crystal structures successfully in several crystal structure prediction (CSP) investigations in recent years⁴, including in the series of blind tests organised by the Cambridge Crystallographic Data Centre^5,6 and in the prediction of the crystal structures of pharmaceutically-relevant molecules^7,8.

We present a summary of CrystalPredictor, focussing on improvements to the lattice energy evaluation that the most recent blind test⁹, as well as our own investigations into a variety of flexible polymorphic molecules, has prompted. These improvements aim to 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 discuss the smoothing of the intramolecular potential in a Non-Uniform context¹⁰; an innovation in CrystalPredictor II that allows the most efficient use of computational effort to cover a flexible molecule’s conformational space. We use blind test molecule 26 as an example, as well as short case studies on the polymorphic landscapes of Bromhexine HCl and Aripiprazole.

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(6) Bardwell, D. A.; Adjiman, C. S.; Arnautova, Y. A.; Bartashevich, E.; Boerrigter, S. X. M.; Braun, D. E.; Cruz-Cabeza, A. J.; Day, G. M.; Della Valle, R. G.; Desiraju, G. R.; van Eijck, B. P.; Facelli, J. C.; Ferraro, M. B.; Grillo, D.; Habgood, M.; Hofmann, D. W. M.; Hofmann, F.; Jose, K. V. J.; Karamertzanis, P. G.; Kazantsev, A. V.; Kendrick, J.; Kuleshova, L. N.; Leusen, F. J. J.; Maleev, A. V.; Misquitta, A. J.; Mohamed, S.; Needs, R. J.; Neumann, M. A.; Nikylov, D.; Orendt, A. M.; Pal, R.; Pantelides, C. C.; Pickard, C. J.; Price, L. S.; Price, S. L.; Scheraga, H. A.; van de Streek, J.; Thakur, T. S.; Tiwari, S.; Venuti, E.; Zhitkov, I. K. Acta Crystallogr B 2011, 67, 535.

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