In addition to providing very rapid geometry optimizations, molecular mechanics models
can also be used to perform conformer searches. Such calculations can be performed using
either PCModel or mengine. In the latter case creating the conpcm file for a conformer
search is more complicated than for a geometry optimization. For this reason, the utility
code named searchme was created (see page 2 for how to make and install this code). To
provide examples of what searchme does, some example PCModel input files are provided as
Supporting Information (in directory conformer_search). To run each example, enter the
command searchme, and give the name of the PCModel file when prompted.
The first example is n-butane. Although there are three C-C bonds in this molecule, only one of these bonds is deemed searchable. This is because rotation of a terminal methyl group, which is 3-fold symmetric, does not normally produce new conformers and is not considered by the search algorithm.
The second example is a rigid, dimethylated naphthalene. The searchme code detects this and stops with a message stating that searching this molecule is not necessary.
The third example has 21 searchable bonds. The searchme code detects this and stops with a message that this structure is too flexible to search. This raises an important point. When the conformational space becomes too large, it is not possible to evaluate all of it in a doable time frame. In this example, if it is assumed that that each rotatable bond has three possible rotamers, then there are 321 = 3,486,784,401 possible conformers. The searchme code will warn the user for any structure when there are ≥ 9 searchable bonds, ≥ 39 = 19,683 possible conformers, write the conpcm file and stop. If the user wishes to proceed, then they can start the search by running mengine. If there are more than 20 searchable bonds, no conpcm file is written.