Date Published: August 01, 2016
Publisher: International Union of Crystallography
Author(s): Anthony M. Reilly, Richard I. Cooper, Claire S. Adjiman, Saswata Bhattacharya, A. Daniel Boese, Jan Gerit Brandenburg, Peter J. Bygrave, Rita Bylsma, Josh E. Campbell, Roberto Car, David H. Case, Renu Chadha, Jason C. Cole, Katherine Cosburn, Herma M. Cuppen, Farren Curtis, Graeme M. Day, Robert A. DiStasio Jr, Alexander Dzyabchenko, Bouke P. van Eijck, Dennis M. Elking, Joost A. van den Ende, Julio C. Facelli, Marta B. Ferraro, Laszlo Fusti-Molnar, Christina-Anna Gatsiou, Thomas S. Gee, René de Gelder, Luca M. Ghiringhelli, Hitoshi Goto, Stefan Grimme, Rui Guo, Detlef W. M. Hofmann, Johannes Hoja, Rebecca K. Hylton, Luca Iuzzolino, Wojciech Jankiewicz, Daniël T. de Jong, John Kendrick, Niek J. J. de Klerk, Hsin-Yu Ko, Liudmila N. Kuleshova, Xiayue Li, Sanjaya Lohani, Frank J. J. Leusen, Albert M. Lund, Jian Lv, Yanming Ma, Noa Marom, Artëm E. Masunov, Patrick McCabe, David P. McMahon, Hugo Meekes, Michael P. Metz, Alston J. Misquitta, Sharmarke Mohamed, Bartomeu Monserrat, Richard J. Needs, Marcus A. Neumann, Jonas Nyman, Shigeaki Obata, Harald Oberhofer, Artem R. Oganov, Anita M. Orendt, Gabriel I. Pagola, Constantinos C. Pantelides, Chris J. Pickard, Rafal Podeszwa, Louise S. Price, Sarah L. Price, Angeles Pulido, Murray G. Read, Karsten Reuter, Elia Schneider, Christoph Schober, Gregory P. Shields, Pawanpreet Singh, Isaac J. Sugden, Krzysztof Szalewicz, Christopher R. Taylor, Alexandre Tkatchenko, Mark E. Tuckerman, Francesca Vacarro, Manolis Vasileiadis, Alvaro Vazquez-Mayagoitia, Leslie Vogt, Yanchao Wang, Rona E. Watson, Gilles A. de Wijs, Jack Yang, Qiang Zhu, Colin R. Groom.
The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.
The ability to predict or explore the solid-state properties of molecules has long been a central aim of computational chemistry and materials science. The ultimate goal of crystal structure prediction (CSP) methods is to be able to explore the possible polymorphs, co-crystals, salts, hydrates etc. of a molecule based solely on minimal information such as its two-dimensional chemical diagram. This information could be used to predict or design novel solid forms, or determine the chance of undesirable polymorphs or solid forms occurring. The latter application of CSP methods is of particular importance for active pharmaceutical ingredients, due to the time and material cost of experimental solid-form screening and the serious consequences of unforeseen polymorphism or alternative solid forms.
Previous blind tests largely followed the same format with the number and complexity of the target systems increasing over the years. Following dialogue with the CSP community in early 2014, a number of changes were made to the organization of the sixth blind test, which are outlined in the following subsections.
There are a wide variety of approaches to predicting organic crystal structures. The larger number of submissions in this blind test has seen a number of new approaches being applied in a blind test for the first time. Broadly speaking, the CSP process can be broken down into a series of steps:
The sixth blind test has been the biggest to date: 25 distinct submissions were received, of which seven were full submissions, 14 attempted some of the targets, and four involved re-ranking structures generated using another method (by another team). This compares to 15 submissions in total in the previous blind test. Table 2 ▸ lists those who contributed to each submission along with a very brief summary of the methods employed, while Tables S10 and S11 in the supporting information provide a more detailed summary of the methods employed. The supporting-information document also contains details on access to computational data resulting from the blind test.
The sixth blind test of organic CSP methods has been the biggest to date, with 21 submissions attempting to predict one or more of the five target systems, and four submissions re-ranking other predictions with different methods. The range of methods and approaches show the development of the field, with progress in the treatment of conformational flexibility in molecules, wider use of ab initio or ab initio-based methods for optimizing and ranking the final structures, as well as more well defined and systematic protocols for performing CSP calculations.