For many of the molecules we are exploring, if we generate a set of conformers, we often find that one or more of the conformers have lower energies than the energy of the single conformer obtained when we select the "Calculate lowest energy conformer" option.
This issue was posted last week but still hasn't been answered so I thought an example might help. For the attached molecule, calculating the lowest energy conformer using all default options yields a structure with reported energy 27.28 kcal/mol. If we instead generate 10 conformers, again using all default options, one of the conformers has an energy of 26.7 kcal/mol. Changing the optimization limit option to "Very strict" and selecting the "Hyperfine" option does not solve the problem; in this case, the lowest energy conformer is reported as 25.96 kcal/mol, while if we generate 10 conformers three of them have energies lower than this. For larger, more complex, molecules these differences are often much larger.
Why isn't the lowest energy conformer the lowest energy conformer?
Using MarvinSketch 126.96.36.199