I. Introduction to Conformation Searching

6Example: CycloheptadecaneThe objective of the cycloheptadecane paper [M. Saunders, K. N. Houk, Y.-D. Wu, W. C. Still, M. Lipton, G.Chang, and W. C. Guida, J. Am. Chem. Soc. 1990, 112, 1419-1427] is to benchmark various conformation searchingmethods. The authors wanted to find out which methods could find most of the low energy conformers ofcycloheptadecane (within 3 kcal/mol of the global minimum). For each method, the authors compiled how manyconformers were located and how much computer (CPU) time the calculation took.A typical cycloheptadecane conformer is shown in Figure 8. Table 4 summarizes the numbers of low-energyconformers of cycloheptadecane found using the MM2 force field.Figure 8. A typical cycloheptadecane conformer.Table 4. Numbers of conformations of cycloheptadecane found relative to the global minimum.within 1 kcal/mol within 2 kcal/mol within 3 kcal/mol11 69 262Five different types of methods were employed for the conformation search: stochastic (random) cartesiancoordinate searches, systematic torsional tree searches, Monte Carlo torsional searches, distance geometry methods,and molecular dynamics. A summary of the results is given in Table 5.Table 5. Summary of conformation searching methods for cycloheptadecane.Method# Low EnergyConformers Found(% of total)CPU time(days)Stochastic Cartesian222Coordinate(85%)Stochastic Cartesian178Coordinate - improved(68%)Torsional Tree Search I 138(53%)Torsional Tree Search II 211(81%)Monte Carlo I 237(90%)Monte Carlo II 249(95%)Distance Geometry 176(67%)Molecular Dynamics 169(65%)CPU time/conformer90 0.4115 0.109 0.06530 0.1430 0.1330 0.1230 0.1730 0.18Note that not only is it important for a conformation search to locate low-energy conformers quickly, but it is alsoimportant that the search be able to find a significant proportion of the total. Therefore, while the distance geometryand molecular dynamics methods are not too much slower than some of the other methods, that they find less than70% of the total conformers is problematic. For this system, Monte Carlo methods provide a good combination ofefficiency and completeness, locating over 90% of the conformers with a time per conformer of 0.12-0.13.