Reducing crystal structure overprediction of ibuprofen with large scale molecular dynamics simulations

Abstract

The control of the crystal form is a central issue in the pharmaceutical industry. The identification of putative polymorphs through Crystal Structure Prediction (CSP) methods is based on lattice energy...

Rationalising the difference in crystallisability of two sulflowers using efficient in silico methods

“…An initial attempt was pursued using density and potential energy as CVs, in line with the previous studies in ref. 15 and 16. However, enhancing density fluctuations mainly induces the exploration of states that are isotropically compressed or expanded with respect to the starting crystal cell, making it a sub-optimal setup for both PSC and sulflower as they display an anisotropic resistance to stress.…”

“…The 20 lowest energy structures of the two CSP_0 sets were subjected to the finite-temperature reduction described in ref. 15 and 16. The 20 structures represent approximately the 5 kJ mol −1 lowest energy structures in both systems, and include a diversity of structures and all the local intermolecular environment discussed in section 3.2.…”

“…Following the procedure in ref. 16, to identify phase transitions along the trajectories, we monitored the distance RMSD 43 with respect to the initial structure. In addition, to automatically detect transitions between similar geometries not captured by the distance RMSD, we performed a cluster analysis every 0.5 kJ mol −1 of work.…”

“…In support of this view, it was shown that the ensemble of configurations explored by a single polymorph at ambient temperature can correspond to multiple lattice energy minima 14 . For these reasons, the equilibration of CSP generated structures at 300 K and 1 bar, has been used as a valuable tool to reduce overprediction 15,16 .…”

“…14 For these reasons, the equilibration of CSP generated structures at 300 K and 1 bar, has been used as a valuable tool to reduce overprediction. 15,16…”