COSMOconf

COSMOconf is a flexible tool box for conformer generation. It enables you to use pre-defined procedures that are optimized for the generation of the most relevant conformers for COSMO-RS.

Based on a unique computational approach, COSMOconf reduces the vast conformational space to a small set of relevant conformations. Unlike most other conformational generators, it is designed to find the relevant conformations in the gas phase, and polar and non-polar solvents.

Key features

  • Automatic conformer selection by relevance to the chemical potential (μ-clustering) in diverse solvents
  • Good accuracy and robustness due to use of density functional theory calculations
  • Large molecules, more than 100 atoms are feasible
  • User-defined conformational search schemes for full flexibility
  • Command line version available for automated batch processing

What is a conformer and how to deal with it?

Conformers are stereoisomers which can be interconverted by rotations about formally single bonds, and each conformer can have a different energy, polarity and hydrogen bonding capacity. Because these properties are essential for the interactions and are the basis for COSMO-RS predictions, the correct conformational average should be used to achieve optimal prediction accuracy. Using only a single conformation can cause significant errors. COSMOtherm calculates the relative Boltzmann statistics in the mixture under consideration and automatically uses the correct conformer ensemble. The aspirin example in the table below shows the influence of the solvent on the population of the conformers. The conformation with hydrogen bond (c2) has nearly no importance in water, but cannot be neglected in hexane.

Conformer population of aspirin [%] at 25 °C

 

c0

c1

c2

water

48.0

51.0

1.0

hexane

57.9

17.6

24.5

logP (octanol / water partitioning)

compound

number of conformers

all conformers

one conformer a

experimental b

oxalic acid

4

0.05

1.25

-0.81

1,2-diaminoethane

3

-1.11

-1.42

-1.31

mandelic acid

6

1.23

0.57

0.74

2-aminoethanol

8

-1.10

-0.75

-1.31

ethylene glycol

5

-1.31

-1.15

-1.36

2-fluorophenol

2

1.80

1.99

1.71

Total RMSE

 

0.42

0.89

 

a the conformer with the lowest COSMO energy has been used
b Hansch, C. et al. (1995) or Medchem Database 2008 or http://www.cdc.gov/niosh/ipcsneng/neng0529.html

Limitations

Due to the complexity of the problem there is no simple method which works for every purpose. COSMOconf offers automated procedures, which will give good results on average. Still it is a heuristic method and thus might miss relevant conformations by chance.

System Requirements

COSMOconf needs TURBOMOLE 6.5 or newer and will not work with
third party quantum chemistry suits.

Platform

TURBOMOLE

PERL

Windows 64

Version 6.5 (TmoleX 3.4) or newer

not required

Linux 64

Version 6.5 (TmoleX 3.4) or newer

Version 5.5 or newer

MacOS 10.8 or newer

Version 6.5 (TmoleX 3.4) or newer

Version 5.5 or newer