The recent study by Merck & Co, Inc. also investigated the application of GRACE to predict the crystal structures of MK-8876, an HCV site NS5B site D inhibitor. The GRACE software failed in predicting the crystal structure for MK-8876 since the candidate structure matching the experimental form was ranked 2290th by the tailor-made force field and was dropped from the workflow. Our calculations correctly predicted the experimental structure, corresponding to rank 10 of the predicted structure (Figure ). The relative energy of the experimental structure of MK-8876 compared to the predicted global minimum varies between 0.1 to 1.5 kcal/mol with different DFT functionals (Figure ), and the gap increased slightly at room temperature (Figure (g) in SI), indicating the possibility for the existence of other polymorphs with competitive stability. This is in line with experimental evidence suggesting other metastable forms. LY156735, a potent and selective melatonin agonist (MA) investigated for the treatment of insomnia and circadian rhythm disorders, showed some unusual crystallization behavior among the R and S enantiomers. While the inactive enantiomer, S-MA, was found to crystallize in at least two anhydrous polymorphic forms (form 1 and 2), with form 2 about 0.7 kcal/mol more stable than form 1, the active enantiomer, R-MA, was found to crystallize only in form 1 despite extensive efforts. In addition, another racemate structure, form RS-MA, was also characterized in the prior work. A prior CSP study predicted form 2 to be more stable than form 1, with the racemate form in between. Our CSP calculations predicted all three forms and ranked them among the top ten lowest energy structures (Figure (e)). Form 2 is correctly predicted to be about 1.0 kcal/mol more stable than form 1 according to r 2 SCAN-D3 and PBE0-MBD functionals, with the energy of the racemate structure in between (Figure ). Interestingly, our calculations also suggested a few other competitive structures, some of which were also predicted in the prior study. A novel racemate candidate structure in the P21/c space group with different hydrogen bond networks was predicted to be the most stable form at 0K but became less stable at room temperature (Figure (i) in SI). These results indicate that the polymorphic landscape of this molecule is perhaps more complex than what is currently known experimentally.