Towards crystal structure prediction of complex organic compounds--a report on the fifth blind test.

Following on from the success of the previous crystal structure prediction blind tests (CSP1999, CSP2001, CSP2004 and CSP2007), a fifth such collaborative project (CSP2010) was organized at the Cambridge Crystallographic Data Centre. A range of methodologies was used by the participating groups in order to evaluate the ability of the current computational methods to predict the crystal structures of the six organic molecules chosen as targets for this blind test. The first four targets, two rigid molecules, one semi-flexible molecule and a 1:1 salt, matched the criteria for the targets from CSP2007, while the last two targets belonged to two new challenging categories - a larger, much more flexible molecule and a hydrate with more than one polymorph. Each group submitted three predictions for each target it attempted. There was at least one successful prediction for each target, and two groups were able to successfully predict the structure of the large flexible molecule as their first place submission. The results show that while not as many groups successfully predicted the structures of the three smallest molecules as in CSP2007, there is now evidence that methodologies such as dispersion-corrected density functional theory (DFT-D) are able to reliably do so. The results also highlight the many challenges posed by more complex systems and show that there are still issues to be overcome.

Investigation of water structure in nafion membranes by infrared spectroscopy and molecular dynamics simulation.

The structure and interactions of water species in hydrated Nafion membranes as a function of water content were investigated on the basis of medium-infrared spectral analysis and molecular dynamics (MD) simulations. The spectral decomposition of the FT-IR data in the stretching OH region was performed on different levels of hydration of the sulfate functional groups (lambdaH2O/RSO3- = 2-22). Quantum mechanical calculations of two model systems [perfluoroethanesulfonic acid/(H2O)6 cluster] and a [perfluorobutanesulfonic acid/(H2O)6 crystal] were carried out in order to account for the band assignments of Nafion in the stretching OH region (2500-4000 cm-1). Our findings indicated that the secondary structure of water species in Nafion can be accurately explained in terms of our reactive force field for water. The distinction between "surface" and "bulk" water contributions in Nafion membrane pores is proposed along with a quantitative estimate of the different types of OH groups present in the system. The average pore size was calculated and supported by the spectral results.

Significant progress in predicting the crystal structures of small organic molecules--a report on the fourth blind test.

We report on the organization and outcome of the fourth blind test of crystal structure prediction, an international collaborative project organized to evaluate the present state in computational methods of predicting the crystal structures of small organic molecules. There were 14 research groups which took part, using a variety of methods to generate and rank the most likely crystal structures for four target systems: three single-component crystal structures and a 1:1 cocrystal. Participants were challenged to predict the crystal structures of the four systems, given only their molecular diagrams, while the recently determined but as-yet unpublished crystal structures were withheld by an independent referee. Three predictions were allowed for each system. The results demonstrate a dramatic improvement in rates of success over previous blind tests; in total, there were 13 successful predictions and, for each of the four targets, at least two groups correctly predicted the observed crystal structure. The successes include one participating group who correctly predicted all four crystal structures as their first ranked choice, albeit at a considerable computational expense. The results reflect important improvements in modelling methods and suggest that, at least for the small and fairly rigid types of molecules included in this blind test, such calculations can be constructively applied to help understand crystallization and polymorphism of organic molecules.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

Molecular dynamics simulation of hydrated Nafion with a reactive force field for water.

We apply a newly parameterized central force field to highlight the problem of proton transport in fuel cell membranes and show that central force fields are potential candidates to describe chemical reactions on a classical level. After a short sketch of the parameterization of the force field, we validate the obtained force field for several properties of water. The experimental and simulated radial distribution functions are reproduced very accurately as a consequence of the applied parameterization procedure. Further properties, geometry, coordination, diffusion coefficient and density, are simulated adequately for our purposes. Afterwards we use the new force field for the molecular dynamics simulation of a swollen polyelectrolyte membrane similar to the widespread Nafion 117. We investigate the equilibrated structures, proton transfer, lifetimes of hydronium ions, the diffusion coefficients, and the conductivity in dependence of water content. In a short movie we demonstrate the ability of the obtained force field to describe the bond breaking/formation, and conclude that this force field can be considered as a kind of a reactive force field. The investigations of the lifetimes of hydronium ions give us the information about the kinetics of the proton transfer in a membrane with low water content. We found the evidence for the second order reaction. Finally, we demonstrate that the model is simple enough to handle the large systems sufficient to calculate the conductivity from molecular dynamics simulations. The detailed analysis of the conductivity reveals the importance of the collective moving of hydronium ions in membrane, which might give an interesting encouragement for further development of membranes.

Crystal structure prediction of small organic molecules: a second blind test.

The first collaborative workshop on crystal structure prediction (CSP1999) has been followed by a second workshop (CSP2001) held at the Cambridge Crystallographic Data Centre. The 17 participants were given only the chemical diagram for three organic molecules and were invited to test their prediction programs within a range of named common space groups. Several different computer programs were used, using the methodology wherein a molecular model is used to construct theoretical crystal structures in given space groups, and prediction is usually based on the minimum calculated lattice energy. A maximum of three predictions were allowed per molecule. The results showed two correct predictions for the first molecule, four for the second molecule and none for the third molecule (which had torsional flexibility). The correct structure was often present in the sorted low-energy lists from the participants but at a ranking position greater than three. The use of non-indexed powder diffraction data was investigated in a secondary test, after completion of the ab initio submissions. Although no one method can be said to be completely reliable, this workshop gives an objective measure of the success and failure of current methodologies.