version date: 1 December 2006 Chlorpromazine(9a) (9b) (9c) CH2COOH Indomethacin(10a) (10b) (10c) Fig 6 Drug structures: 3D, nonoptimized, and optimized by the program MOPAC (Chem3D) Chlorpromazine(9a),(9b), nonoptimized and(9c)optimized; Indomethacin(10a), (10b), nonoptimized and (10c), optimized C Molecular dynami It was already stated that 3D conformations are not necessarily the most stable ones and that the energy minimization process is interrupted when structure variations imply small changes in energy. Graph I shows that this stable" conformation may be separated from another, even more stable that the minimizing process is unable to overcame. In this instance, the most stable conformation, with a minimal global energy, has to be identified by comparison of different conformations and the corresponding energy values <www.iupac.org/publications/cd/medicinalchemistry/>8 N S Cl N Chlorpromazine (9a) (9b) (9c) N CH3 O Cl CH2COOH Indomethacin (10a) (10b) (10c) Fig. 6 Drug structures: 3D, nonoptimized, and optimized by the program MOPAC (Chem3D). Chlorpromazine (9a), (9b), nonoptimized and (9c) optimized; Indomethacin (10a), (10b), nonoptimized and (10c), optimized. C. Molecular dynamics It was already stated that 3D conformations are not necessarily the most stable ones and that the energy minimization process is interrupted when structure variations imply small changes in energy. Graph 1 shows that this “stable” conformation may be separated from another, even more stable that the minimizing process is unable to overcame. In this instance, the most stable conformation, with a minimal global energy, has to be identified by comparison of different conformations and the corresponding energy values.10,14 <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006