MacroModel Example: Conformational Search Using MCMM

An example command file appears below for a conformational search calculation that uses the MCMM search method. Descriptions of the opcodes in the file follow.

mcmm.mae
mcmm-out.mae
 FFLD      10      1      0      1     1.0000     0.0000     0.0000     0.0000
 BDCO       0      0      0      0    41.5692 99999.0000     0.0000     0.0000
 READ       0      0      0      0     0.0000     0.0000     0.0000     0.0000
 MCMM     100      0      0      0     0.0000     0.0000     0.0000     0.0000
 MCNV       2      4      0      0     0.0000     0.0000     0.0000     0.0000
 MCSS       2      0      0      0    50.0000     0.0000     0.0000     0.0000
 MCOP       1      0      0      0     0.0000     0.0000     0.0000     0.0000
 DEMX       0    166      0      0    50.0000   100.0000     0.0000     0.0000
 MSYM       0      0      0      0     0.0000     0.0000     0.0000     0.0000
 COMP       1      2      3      4     0.0000     0.0000     0.0000     0.0000
 COMP       5      6      7      9     0.0000     0.0000     0.0000     0.0000
 COMP      10     14     15     16     0.0000     0.0000     0.0000     0.0000
 COMP      17     25     26     27     0.0000     0.0000     0.0000     0.0000
 COMP      28     29     30     31     0.0000     0.0000     0.0000     0.0000
 TORS       1     14      0      0     0.0000   180.0000     0.0000     0.0000
 TORS       6     25      0      0     0.0000   180.0000     0.0000     0.0000
 TORS      14     15      0      0     0.0000   180.0000     0.0000     0.0000
 TORS      15     16      0      0     0.0000   180.0000     0.0000     0.0000
 TORS      25     26      0      0     0.0000   180.0000     0.0000     0.0000
 CONV       2      0      0      0     0.0500     0.0000     0.0000     0.0000
 MINI       9      0    500      0     0.0000     0.0000     0.0000     0.0000

FFLD: Force field selection. Arg1 defines the force field used in the calculation (in this case MMFF94). Arg2 defines the electrostatic treatment for the calculation. In this case a constant dielectric is used. Arg4 is MMFF94 specific: arg4=1 defines the MMFF94s version of the force field, ensuring planarity around delocalized sp² nitrogens.

BDCO: Use the Bond Dipole CutOff (BDCO) method for truncating electrostatic interactions. Arg5 and arg6 are used to specify the cutoffs used for charge-dipole and charge-charge interactions, respectively.

READ: Read the input file.

MCMM: Use Monte Carlo Multiple Minimum searching. Arg1 defines the number of MC steps for the search.

MCNV: Sets the number of degrees of freedom to be varied at each MC step. If arg1 and arg2 differ, the search varies a random number of degrees of freedom between the numbers defined in arg1 and arg2. We recommend setting arg1=2 and arg2=maximum number of degrees of freedom.

MCSS: Select starting structure for the search steps. Arg1=2 defines use-directed selection of starting structures, where the least used structures will be used as starting geometries, as long as they are low enough in energy (as defined in arg5). This is more efficient in exploring new areas of the potential energy surface than, for instance, a random-walk starting geometry scheme. Arg5 gives the energy window for selecting a new starting structure. The new starting structure must be within arg5 kJ/mol of the lowest energy conformer found in the search.

MCOP: Monte Carlo options determine what and how often data is written to the log file. Arg1=1 ensures printing to the log file at every search step.

DEMX: This command is used to prevent saving of high-energy conformers during the search. Arg5 defines the allowed energy window above the currently found global minimum. New conformers that are not within arg5 kJ/mol will be discarded. Additionally, a preliminary energy test can be performed during the energy minimization, to ensure that a reasonable structure has been found. Arg2 sets the number of energy iterations to be performed before the preliminary test (a good value is approximately 1/3 of the total number of energy iterations), while arg6 defines the energy above which conformers will be discarded (a value of about 1.5–2 times arg5 is recommended).

MSYM: Invokes the numbering symmetry library mmsym, which automatically and more generally identifies a suitable numbering order for use in comparing molecular conformations.

COMP: Arg1-arg4 list the atom numbers of atoms to be used in structural comparison with all previously found conformers. A maximum of 200 atoms can be used in the comparisons. For arg1=0, all heavy atoms are compared. By default, structures that have equivalent atoms separated by more than 0.25 Å upon superposition are considered different.

TORS: Defines the variable torsions in the molecule. Arg1 and arg2 are the atom numbers of the two central atoms defining a variable torsion. Arg5 and arg6 define the minimum and maximum dihedral angle variations (in both directions).

CONV: Defines convergence criteria. Arg1=2 specifies derivative convergence (default criterion is 0.05 kJ/mol-Å, and this value is set in arg5).

MINI: Starts the minimization. Arg1 defines the type of minimization algorithm to be used. Arg1=9 means that Truncated Newton-Raphson Conjugate Gradient will be used. In arg3, the number of minimization steps is defined. Arg3 can be set to a large number since the calculation automatically stops as soon as the convergence criterion has been reached.