Crystal Structure Prediction (CSP) of Pharmaceutical Drugs

CSP is of importance in the development of new human drugs where the crystal structure plays a crucial role in drug formulation, stability and the patent process. A large number of drugs are lost in the pipeline due to the lack of appropriate formulation, and finding alternative formulation strategies is costly and inefficient. Therefore, in silico exploration of alternative formulation strategies by predicting crystal structures a priori can revolutionize drug formulation and improve drug pipeline yields considerably. Our MGAC approach has demonstrated that its search capabilities using genetic algorithms are second to none; consistently MGAC finds the correct structure when an accurate representation of the potential energy surface is provided. Our current focus is in using first principles methods (DFT-D) to improve the accuracy of MGAC. In this context we work in developing better algorithms, exploring new hardware devices, like GPUs and accelerators, and large scale computing infrastructures like the Open Science Grid. Our ultimate goal is using MGAC in practical applications for improving the design of co-crystals of pharmaceutical interest.



Exemplar Publications

  • Kim S, Orendt AM, Ferraro MB, Facelli JC (2009). Crystal Structure Prediction (CSP) of Flexible Molecules using Parallel Genetic Algorithms with a Standard Force Field. J Comput Chem, 30, 1973-1985.
  • Bardwell DA, Adjiman CS, Arnautova YA, Bartashevich E, Boerrigter SX, Braun DE, Cruz-Cabeza AJ, Day GM, Della Valle RG, Desiraju GR, van Eijck BP, Facelli JC, Ferraro MB, Grillo D, Habgood M, Hofmann DW, Hofmann F, Jose KV, Karamertzanis PG, Kazantsev AV, Kendrick J, Kuleshova LN, Leusen FJ, Maleev AV, Misquitta AJ, Mohamed S, Needs RJ, Neumann MA, Nikylov D, Orendt AM, Pal R, Pantelides CC, Pickard CJ, Price LS, Price SL, Scheraga HA, van de Streek J, Thakur TS, Tiwari S, Venuti E, Zhitkov IK (2011). Towards crystal structure prediction of complex organic compounds--a report on the fifth blind test. Acta Crystallogr B, 67(Pt 6), 535-51.
  • Lund AM, Orendt AM, Pagola GI, Ferraro MB, Facelli JC (2013). Optimization of Crystal Structures of Archetypical Pharmaceutical Compounds: A Plane-Wave DFT-D Study Using Quantum Espresso. Cryst Growth Des, 13(5), 2181-2189.
  • Lund AM, Pagola GI, Orendt AM, Ferraro, MB, Facell, JC (2015). Crystal structure prediction from first principles: The crystal structure of glycine. Chemical Physics Letters, 626, 20-24.

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