Now in Nature

"Crystal Structure Predictions you can TRHu(ST) " 

Press Release​​​​

Free-energy landscape of radiprodil hydrate and anhydrate forms at 298.15 K and relative humidity of 50%

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Together with visionary customers, we embarked on a journey to transform Crystal Structure Prediction (CSP) from an academic playground into a reliable and quantitative engineering tool twenty years ago.

Today we are proud to announce that we have finally arrived. With our new TRHu(ST) method, now published in Nature (also see our press release), the free energy differences of hydrates and anhydrates can be calculated with known error bars as a function of temperature and relative humidity, thus confirming beyond doubt candidates for late-appearing forms or disappearing polymorph cases.

On our journey, we have passed many milestones (full publication list), including the publication of the first accurate solid-state dispersion correction for DFT  in 2005, the machinery for the generation of tailor-made force fields in 2008, the 4-out-of-4 success rate in the 4th blind test on crystal structure prediction in 2008, more excellent results in the 5th and 6th blind tests in 2011 and 2016, the first example for rational crystallization experiment design to make new crystal forms in 2015, the first meta-study on a large set of industrial CSP studies in 2018 and economy of scale to bring CSP closer to drug discovery in 2022. However,  TRHu(ST) feels different than just another milestone. TRHu(ST) is a landmark that announces the beginning of a new era of crystal modelling.

If we have got this far, this is only because we have never been alone on our journey. Our clients have always been there with us right from the start. Our early customers, who believed in our ability to innovate when modern crystal structure prediction was nothing but a spark on the horizon; our loyal customers, who came back year after year with compounds corresponding to our abilities at that time to fund further software development through software sales and contract research; and our ambitious customers, who keep pushing us out of our comfort zone. We thank all of them for their trust, patience and inspiration.


Crystal structure prediction is not the Holy Grail of crystallography anymore, but simply a proven technique. Our journey is not yet over. TRHu(ST)  is a stepping stone into a bright and promising future.​ The next promise carries other names such as in silico solid-state form selection or digital materials design. We are still hungry. We have grown and matured. All the while, with our customers still by our side.

Our scientific publications

Mortazavi M., Hoja J., Aerts L., Quéré L., van de Streek J., Neumann M.A. & Tkatchenko A.
Computational Polymorph Screening Reveals Late-Appearing and Poorly-Soluble Form of Rotigotine
Commun Chem 2: 70 (2019)

​Neumann M.A. & van de Streek J.
How Many Ritonavir Cases Are There Still out There?
Faraday Discuss. Vol 211: 441-458. (2018) Open Access  

Neumann M.A., van de Streek J., Fabbiani F.P.A., Hidber P. & Grassmann O.
Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening
Nature Communications 6: 7793 (2015)

Mattei A. & al. 
Efficient Crystal Structure Prediction for Structurally Related Molecules with Accurate and Transferable Tailor-Made Force Fields

J. Chem. Theory Comput. 18, 9, 5725–5738 (2022)

Braun D.E., McMahon J.A., Bhardwaj R., Nyman J., Neumann M.A., van de Streek J. & Reutzel-Edens S.M.
Inconvenient Truths about Solid Form Landscapes Revealed in the Polymorphs and Hydrates of Gandotinib
Cryst. Growth Des. 19: 2947-2962 (2019)

Woollam G.R., Neumann M.A., Wagner T. & Davey R.J.
The importance of configurational disorder in crystal structure prediction: the case of loratadine
Faraday Discuss. Vol 211: 209-234 (2018)

Kendrick J., Stephenson G.A., Neumann M.A. & Leusen F.J.J.
Crystal structure prediction of a flexible molecule of pharmaceutical interest with unusual polymorphic behaviour
Cryst.Growth and Design 13, 581-589 (2013)

Neumann M.A. & Perrin M-A.
Can crystal structure prediction guide experimentalists to a new polymorph of paracetamol?
CrystEngComm 111: 2475-2479 (2009)

Hoja J. & al. Reliable and practical computational description of molecular crystal polymorphs
Science Advances 11 Jan 2019:Vol. 5, no. 1, eaau3338

Reilly A. & al. Report on the sixth blind test of organic crystal structure prediction methods
Acta Crystallographica. Section B: Structural Science 72: 439-459 (2016)

Bardwell D. & al.
Towards crystal structure prediction of complex organic compounds—a report on the fifth blind test
Acta Crystallographica. Section B: Structural Science 67: 535-551 (2011)

Kendrick J., Leusen F.J.J., Neumann M.A. & van de Streek J.
Progress in crystal structure prediction
Chemistry: A European Journal 17: 10736-44 (2011)

Chan H.C.S., Kendrick J. & Leusen F.J.J.
Molecule IV, a benchmark crystal-structure-prediction sulfonamide: are its polymorphs predictable?
Angewandte Chemie Interlational Edition, 50: 2979-2981 (2011)

Chan H.C.S., Kendrick J. & Leusen F.J.J.
Predictability of the polymorphs of small organic compounds: crystal structure predictions of four benchmark blind test molecules
Physical Chemistry Chemical Physics, 13: 20361-20370 (2011)

Asmadi A., Neumann M.A., Kendrick J., Girard P., Perrin M.A. & Leusen F.J.J.
Revisiting the blind tests in crystal structure prediction: accurate energy ranking of molecular crystals
Journal of Phys. Chem. B, 113: 16303-16313 (2009)

Day G.M. & al.,
Significant progress in predicting the crystal structures of small organic molecules—a report on the fourth blind test
Acta Crystallographica. Section B: Structural Science 65: 107-125 (2008)

Neumann M.A., Leusen F.J.J. & Kendrick J.
A major advance in crystal structure prediction
Angew. Chem. Int. Ed. 47: 2427-2430 (2008)

Sanderson K.
Model predicts structure of crystals
Nature 450: 771 (2007)

Chan H.C.S., Kendrick J., Neumann M.A. & Leusen F.J.J.
Towards ab initio screening of co-crystal formation through lattice energy calculations and crystal structure prediction of nicotinamide, isonicotinamide, picolinamide and paracetamol multi-component crystals
CrystEngComm, 15: 3799-3807 (2013)

Montis R., Hursthouse M.B., Chan H.C.S., Kendrick J. & Leusen F.J.J.
Experimental and theoretical investigations of the polymorphism of 5-chloroacetoxybenzoic acid
CrystEngComm, 14: 1672-1680 (2012)

Willer R.L., Storey R.F., Deschamps J., Parrish D., Kendrick F. & Leusen F.J.J.
Synthesis, prediction, and determination of crystal structures of (R/S)- and (S)-1,6-dinitro-3,8-dioxa-1,6-diazaspiro[4.4]nonane-2,7-dione
Crystal Growth and Design, 12: 5292-5297 (2012)

van de Streek J. & Neumann M.A.
Crystal-structure prediction of pyridine with four independent molecules
CrystEngComm 13: 7135-7142 (2011)

Asmadi A., Kendrick J. & Leusen F.J.J.
Crystal structure prediction and isostructurality of three small organic halogen compounds
Physical Chemistry Chemical Physics, 12: 8571-8579 (2010)

Asmadi A., Kendrick J. & Leusen F.J.J.
Crystal structure prediction and isostructurality of three small molecules
Chemistry – A European Journal, 16: 12701-12709 (2010)

Kendrick J., Gourlay M.D., Neumann M.A. & Leusen F.J.J.
Predicting spontaneous racemate resolution using recent developments in crystal structure prediction
CrystEngComm, 11: 2391-2399 (2009)

Kendrick J., Montis R., Hursthouse M.B. & Leusen F.J.J.
In-silico seeding’: isostructurality and pseudoisostructurality in a family of aspirin derivatives
Crystal Growth and Design, 13: 2906-2915 (2013)

Woollam G.R., Das P.P., Mugnaioli E., Andrusenko I., Galanis A.S., van de Streek J., Nicolopoulos S., Gemmi M. & Wagner T.
Structural Analysis of Metastable Pharmaceutical Loratadine Form II, by 3D Electron Diffraction and DFT+D Energy Minimisation
CrystEngComm (2020) Advance Article

van de Streek J. & Neumann M.A.
Validation of molecular crystal structures from powder diffraction data with dispersion-corrected density functional theory
Acta Crystallographica. Section B: Structural Science 70: 1020-1032 (2014)

Többens D.M., Glinneman J., Cierotti M.R., van de Streek J. & Sheptyakov D.
On the high-temperature phase of barbituric acid
CrystEngComm 14: 3046-3055 (2012)

Gorelic T.E., van de Streek J., Kilbinger A.F.M., Brunklaus G. & Kolb U.
Ab-initio crystal structure analysis and refinement approaches of oligo p-benzaides based on electron diffraction data
Acta Cryst. B68: 171-181 (2012)

Rietveld I.B., Barrio M., Tamarit J.L., Nicolai B., van de Streek J., Mahé N., Céolin R. & Do B.
Dimorphism of the prodrug L-tyrosine ethyl ester: The topological pressure-temperature diagram and the crystal structure of phase II
J. Pharm. Sci., 4774-4782 (2011)

Schmidt M.U. & al.
The thermodynamically stable form of solid barbituric acid: The enol tautomer
Angew. Chem. 50: 7924-7926 (2011)

Bond A.D., Solanko K.A., van de Streek J. & Neumann M.A.
Experimental verification of a subtle low-temperature phase transition suggested by DFT-d energy minimization
CrystEngComm 13: 1768-1771 (2011)

Brüning J., Alig E., van de Streek J. & Schmidt M.U.
The use of dispersion-corrected DFT calculations to prevent an incorrect structure determination from powder data: The case of acetolone, C11H11N3O3
Z. Kristallogr. 226: 476-482 (2011)

Bekö S.L. & al.
X-ray powder diffraction, solid-state NMR and dispersion-corrected DFT calculations to investigate the solid-state structure of 2-ammonio-5-chloro-4-methylbenzenesulfonate
Z. Kristallogr. 225: 382-387 (2010)

van de Streek J. & Neumann M.A.
Validation of experimental molecular crystal structures with dispersion-corrected density functional theory calculations
Acta Crystallographica. Section B: Structural Science 66: 544-58 (2010)