MacroModel Reference Manual - ISP

Chapter 4: Operation CodesThis command is implemented in conjunction with minimization and conformational searches.Only LMCS, MCMM or mixed LMCS/MCMM searches are supported for conformational searchMBAE. Please note that MBAE conformational searches may require the purchase of an additionallicense.Energy difference mode is the only mode permitted for conformational search MBAE. Thevalues of E protein and E ligand are the lowest energies found for any conformer of the protein andligand respectively. ∆E is calculated for each complex conformation saved in the output structurefile using the energy of the current complex conformation for E complex . The number ofoutput structures can be controlled independently of the number of steps performed in thesearch, via arg6 of MCOP. MBAE can also be used in conjunction with COPY/ALGN and MCOParg7 to pre-position ligands for MBAE conformational searches based on a crystal structure of arelated complex. The .com file for MBAE conformational searches is complex and specific, andconsulting Section 14.2 of the MacroModel User Manual for MBAE searches is recommended.Both minimization and conformational search MBAE calculations may be distributed acrossmultiple processors. If such calculations are carried out in energy difference mode then thecalculation on the receptor is carried out by the parent process prior to distributing the calculationsfor the ligands amongst the processors indicated. Please see the NPRC command for moreinformation. Please note that arg3=2 is not supported for distributed MBAE calculations.A substructure file should be used to specify substructures and various fixed/frozen constraintswithin the receptor.arg1−1Selection of Association Energy modeTurn MBAE off.0 Use Interaction Energy mode.The interaction energy between the ligand and the receptor is calculated using theASET mechanism. For non-covalently bonded receptor/ligand pairs, this correspondsto the nonbonded energy. While a number of sets may be used, the onlyproject properties recorded in the output structure file are those for the interactionsbetween sets 1 and 2.Note:For jobs set up in Maestro, ELST arg1 is set to −1 in the .com file when MBAE is run inInteraction Mode (i.e., when MBAE arg1 is set to 0).1 Use Energy Difference mode.The calculation is performed on the receptor first, then it is carried out on the ligand,and finally it is performed on the complex. All calculations start from the structuresprovided in the input structure file.MacroModel 9.7 Reference Manual 139