When performing a conformational search, how do I judge whether the search has covered the complete conformation space?
For a non-systematic search method (like MCMM, LMCS, or LMC2) there is no single indicator that a search has sampled sufficient conformation space. If you want to ensure that a search is exhaustive, break the search up into blocks of 1000-5000 steps (the exact number will depend on the problem size). Run the first “block” and reminimize the structures to ensure that they are all converged. Then, “seed” the second search with the structures from the first by using the output structure file containing structures from the first search as the input structure file for the second search. Continue this process of running blocks, each seeded with the results of the previous block until a block of steps produces no new low energy structures. For an exhaustive search, run until a block produces no new structures. For more information, see the section “General Guidelines for Convergence” in the MacroModel User Manual (Chapter 4).
