MacroModel Example: Mixed MCMM/Low-Mode Search Using a Substructure File
This example uses the CDK2 structure 1e1v with the co-crystallized ligand cmg. Alternate binding modes of the ligand are sampled using a mixture of torsional moves, low-mode moves, and rotation and translation of the ligand, in a conformational search. This example was prepared with Maestro. A substructure is used, in which the freely moving region includes the ligand and any residues with atoms within 3.0 Å of the ligand. A fixed and frozen region was also set up in the Substructure tab. The conformational search parameters were initially set by using the Perform Automatic Setup button in the CSearch tab. The parameters were then modified using the individual parameter panels in the CSearch tab to arrive at the sample instruction file below. Only torsions in the ligand are being explicitly sampled in this example.
Descriptions of the opcodes not used in the previous conformational search command file examples follow.
subs-mcmm-lmod.mae subs-mcmm-lmod-out.mae FFLD 11 1 0 0 1.0000 0.0000 0.0000 0.0000 EXNB 0 0 0 0 0.0000 0.0000 0.0000 0.0000 BDCO 0 0 0 0 89.4427 99999.0000 0.0000 0.0000 SUBS 0 0 0 0 0.0000 0.0000 0.0000 0.0000 READ 0 0 0 0 0.0000 0.0000 0.0000 0.0000 CRMS 0 0 0 0 10.0000 0.5000 0.0000 0.0000 LMCS 10 0 0 0 0.0000 0.0000 3.0000 6.0000 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 0.5000 0.0000 0.0000 0.0000 DEMX 0 666 0 0 50.0000 100.0000 0.0000 0.0000 COMP 117 121 128 133 0.0000 0.0000 0.0000 0.0000 COMP 136 140 158 162 0.0000 0.0000 0.0000 0.0000 COMP 165 169 174 176 0.0000 0.0000 0.0000 0.0000 COMP 223 225 231 236 0.0000 0.0000 0.0000 0.0000 COMP 439 445 466 470 0.0000 0.0000 0.0000 0.0000 COMP 473 476 482 487 0.0000 0.0000 0.0000 0.0000 COMP 1291 1296 1299 1303 0.0000 0.0000 0.0000 0.0000 COMP 1307 1309 1313 1318 0.0000 0.0000 0.0000 0.0000 COMP 1326 1362 1366 1370 0.0000 0.0000 0.0000 0.0000 COMP 1372 2105 2109 2115 0.0000 0.0000 0.0000 0.0000 COMP 2120 2155 2159 2164 0.0000 0.0000 0.0000 0.0000 COMP 2172 2323 2327 2331 0.0000 0.0000 0.0000 0.0000 COMP 2333 4599 4600 4601 0.0000 0.0000 0.0000 0.0000 COMP 4602 4603 4604 4605 0.0000 0.0000 0.0000 0.0000 COMP 4606 4607 4608 4609 0.0000 0.0000 0.0000 0.0000 COMP 4610 4611 4612 4613 0.0000 0.0000 0.0000 0.0000 COMP 4614 4615 4616 0 0.0000 0.0000 0.0000 0.0000 MSYM 0 0 0 0 0.0000 0.0000 0.0000 0.0000 CHIG 117 119 165 167 0.0000 0.0000 0.0000 0.0000 CHIG 223 439 468 1291 0.0000 0.0000 0.0000 0.0000 CHIG 1311 1364 2107 2157 0.0000 0.0000 0.0000 0.0000 CHIG 2325 0 0 0 0.0000 0.0000 0.0000 0.0000 TORS 4600 4610 0 0 0.0000 180.0000 0.0000 0.0000 TORS 4604 4605 0 0 0.0000 180.0000 0.0000 0.0000 TORS 4605 4606 0 0 0.0000 180.0000 0.0000 0.0000 TORS 4606 4611 0 0 0.0000 180.0000 0.0000 0.0000 MOLS 4633 0 0 0 0.0000 180.0000 0.0000 1.0000 TORC 135 134 132 133 90.0000 180.0000 0.0000 0.0000 TORC 164 163 161 162 90.0000 180.0000 0.0000 0.0000 TORC 1310 1309 1307 1308 90.0000 180.0000 0.0000 0.0000 TORC 2118 2117 2115 2116 90.0000 180.0000 0.0000 0.0000 CONV 2 0 0 0 0.1000 0.0000 0.0000 0.0000 MINI 9 0 1000 0 0.0000 0.0000 0.0000 0.0000
SUBS: With arg1=0 look for an .sbc file that contains information on how the substructure is set up in the system.
MCOP: Arg1=1 print search results every step. Arg5=0.5 specifies that this mixed Monte Carlo/Low-Mode search will attempt Monte Carlo torsional and/or molecular translation moves half the time. The rest of the attempted moves will be generated using low-mode moves.
MOLS: Arg1-4 sepecifies one atom from each molecule to be moved using molecular translation/rotation moves. Arg5 and arg6 specify the minimum and maximum rotation angles while arg7 and arg8 specify the minimum and maximum translation distances.