Docking (Molecular Association) Opcodes

The opcodes in this section are linked below:

MBAE — Multi-ligand Bimolecular Association with Energetics: Embrace

MBAE — Multi-ligand Bimolecular Association with Energetics: Embrace

MBAE invokes an algorithm in which MacroModel performs calculations on a number of pre-positioned ligands with a single receptor. The input structure file must must be a multiple structure file consisting of a receptor followed by each pre-positioned ligand in turn. MBAE works in two modes, interaction mode and energy difference mode. In the former the calculation examines the interaction between the receptor and the ligand, while in the latter the calculation is performed on the receptor, the ligand, and then the complex.

Values calculated for the energy difference mode are given by the equation:

ΔE = Ecomplex − Eligand − Eprotein

This command is implemented in conjunction with minimization and conformational searches. Only LMCS, MCMM or mixed LMCS/MCMM searches are supported for conformational search MBAE. Please note that MBAE conformational searches may require the purchase of an additional license.

Energy difference mode is the only mode permitted for conformational search MBAE. The values of Eprotein and Eligand are the lowest energies found for any conformer of the protein and ligand respectively. ΔE is calculated for each complex conformation saved in the output structure file using the energy of the current complex conformation for Ecomplex. The number of output structures can be controlled independently of the number of steps performed in the search, via arg6 of MCOP. MBAE can also be used in conjunction with COPY/ALGN and MCOP arg7 to pre-position ligands for MBAE conformational searches based on a crystal structure of a related complex. The .com file for MBAE conformational searches is complex and specific, and consulting Conformational Searches With Embrace for MBAE searches is recommended.

Both minimization and conformational search MBAE calculations may be distributed across multiple processors. If such calculations are carried out in energy difference mode then the calculation on the receptor is carried out by the parent process prior to distributing the calculations for the ligands amongst the processors indicated. Please see the NPRC command for more information. 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 constraints within the receptor.

arg1

Selection of Association Energy mode

−1

Turn MBAE off.

0

Use Interaction Energy mode.
 

The interaction energy between the ligand and the receptor is calculated using the ASET mechanism. For non-covalently bonded receptor/ligand pairs, this corresponds to the nonbonded energy. While a number of sets may be used, the only project properties recorded in the output structure file are those for the interactions between 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 in Interaction 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 structures provided in the input structure file.

arg2

Type of calculation being performed

0

Minimization (MINI) calculations are performed.

1

Conformational search calculations are performed.

arg3

Structural output

0

Only the resulting complex structures are recorded.

1

Only the resulting ligand structures extracted from the resulting complex structure are recorded.

2

For Interaction Mode calculations this is the same as arg3 = 0.
 

For Energy Difference calculations, structures are recorded in the following order:
 

Processed Protein structure (no ligand).
 

For each ligand:

  • The processed ligand structure (isolated, no protein).

  • The processed complex structure.
 

For arg3 = 2 the MBAE project properties are recorded with the complex structure only.
 

Arg3 = 2 is not supported for distributed calculations.

arg4

DEBG 510 (Do not enforce properties dependencies)

0

Turns on DEBG 510 (default).

1

Turns off DEBG 510.