Close S O Interactions

IMPROVING FORCE FIELD PARAMETERS FOR SMALL-MOLECULE 

IMPROVING FORCE HELD PARAMETERS EOR SMALL-MOLECULE 

FIGURE 4.6 RMSD box plots of the 130 test set structures using different levels of theory for geometry minimization. The median RMSD is denoted as a horizontal line through each box. The bottom and the top of the box mark the lower and upper quartUe, respectively. The whiskers extend to 1.5 IQR (interquartile range) and the molecules with RMSD larger than that are the outliers, shown with x marks. Source Adapted from Lupyan et al. [37]. Reproduced with permission of Springer. 

FIGURE 4.7 Lowest-energy structures of a CSD molecule (CSD refcode FOKWEI) containing a close S O interaction, minimized with different levels of computational theory. Numerical values to the left of each molecule show the S- 0 distance and SCNC=0 planarity. The RMSD with respect to the CSD conformation is shown to the bottom right of each structure. Source Adapted from Lupyan et al. [37]. Reproduced with permission of Springer. 

Finally, the ultimate objective of this work is to generate conformations that can be repacked in the correct crystal form. To do this, a limited CSP study was performed on axitinib, as follows. First, we took the structures from the conformational search using each force field with the lowest RMSD to the crystal forms 1, VI, XXV, and XLI. These conformations were used as input for the Polymorph Predictor in an attempt to reproduce the crystal forms in the corresponding space groups. Form IV was not considered in this limited study because it has two molecules in the asymmetric unit cell (termed IV and IV ), which makes the computational CSPs substantially more challenging and time consuming. 

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Identification of the problematic interaction In many cases the deficiency in the force field will be clear. For example, in the case of the close S - O interactions it was... 

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