MacroModel Example: Partition Coefficient Estimation
Below is an example of a command file for conducting log Poctanol,water calculations on a series of molecules. It is very similar to that used for multiple minimization of non-conformers.
logP.mae logP-out.mae FFLD 11 1 0 1 1.0000 0.0000 0.0000 0.0000 BDCO 0 0 0 0 41.5692 99999.0000 0.0000 0.0000 SOLV 3 9 0 0 0.0000 0.0000 0.0000 0.0000 LOGP 1 1 1 0 0.0000 0.0000 0.0000 0.0000 BGIN 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 AUTO 0 -1 0 0 0.0000 1.0000 0.0000 0.0000 CONV 2 0 0 0 0.0500 0.0000 0.0000 0.0000 MINI 1 0 5000 0 0.0000 0.0000 0.0000 0.0000 END 0 0 0 0 0.0000 0.0000 0.0000 0.0000
SOLV: Specifies the first, or primary, solvent. Arg2 = 9 corresponds to octanol.
LOGP: Turns on partition coefficient estimation and specifies the second solvent. Arg2 = 1 corresponds to water.
AUTO: Necessary for the proper processing of LOGP calculations. Arg2 = −1 instructs AUTO not to make a list of comparison atoms, and arg6 = 1.0000 indicates that this is a serial calculation.
In the .log file produced when such a calculation is run, a report appears for each ligand processed:
===================================== LOGP(octanol,water) Calculation for ligand # 1 Ligand Name: Case74C LOGP(octanol,water) = 1.41024 =====================================
and a table appears at the end of the .log file:
=====================================
LOGP(octanol,water) Results
Ligand Solvation Free Energies LOGP(octanol,water) Converged
octanol water
kJ/mol. kJ/mol.
1 -26.99 -18.94 1.41 T
2 -20.93 -12.48 1.48 T
3 -20.02 -11.02 1.58 T
4 -29.41 -16.19 2.32 T
...
12 -16.84 -15.40 0.25 T
=====================================
Here, T or F in the Converged column signifies whether or not the minimizations (one in each solvent for each molecule) converged. If they did not converge, the results should not be considered reliable.