Calculated conformer energies for organic molecules with multiple polar functionalities are method dependent: Taxol (case study)

Table 3 NMR/NAMFIS and X-ray structure determined conformations of Taxol evaluated energetically by four force fields in the gas phase, two solvation continuum models with the use of scaled ESP atomic charges; Relative energies, kcal/mol.a

	MMFF			AMBER*			MM2*			MM3*
	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O
1	60.0	57.8	57.5	76.0	74.8	88.5	47.8	43.2	40.1	46.3	41.9	41.9
2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
3	66.1	62.6	61.5	81.6	80.9	86.6	39.2	29.7	25.8	33.2	30.1	30.1
4	22.6	18.0	24.9	21.7	21.5	24.5	24.3	15.2	21.7	28.1	16.4	16.4
5	36.5	31.6	35.3	33.4	30.9	37.8	33.0	28.9	28.5	32.0	27.4	27.4
6^b	23.7	23.0	28.1	20.0	24.9	27.2	30.0	22.6	24.6	28.6	22.9	22.9
7^b	50.2	49.9	60.6	38.8	44.2	53.6	72.4	63.2	72.3	81.3	68.0	68.0

^a Each structure was optimized with the indicated force field and the accompanying GBSA solvation model. [2b]^b Taxol conformations determined in the solid state;¹⁵ optimized using AMBER* with all non-terpenoid core dihedral angles frozen; 6 polar; 7 extended.