Rowan Docs

Solvent-Dependent Conformer Search

A molecule's preferred conformations can change with solvent. Rowan's solvent-dependent conformer search builds one diverse conformer set and evaluates it consistently in several solvents, making it possible to compare populations, ensemble properties, and relative ensemble free energies across environments.

How it works

  1. Rowan generates an initial conformer ensemble based on input settings.
  2. Solvent-aware clustering retains structures that represent low-energy regions across the selected solvents.
  3. Each retained conformer is optimized and scored using the selected multistage optimization settings.
  4. A GFN2-xTB frequency calculation supplies a rigid-rotor/harmonic-oscillator (RRHO) thermal correction.
  5. The workflow applies either the default CPCM-X solvation treatment or an optional COSMO-RS final correction in each solvent.

For conformer ii in solvent ss, the free energy is assembled as

Gi,s=EiMSO+ΔGsolv,i,s+GiRRHO.G_{i,s} = E_i^{\mathrm{MSO}} + \Delta G_{\mathrm{solv},i,s} + G_i^{\mathrm{RRHO}}.

With the CPCM-X final correction, solvent-dependent single-point energies provide the solvation treatment. With COSMO-RS, Rowan calculates one DFT COSMO surface for each retained conformer and obtains solvation free energies for every selected solvent.

Within each solvent, Rowan converts the conformer free energies into Boltzmann populations at 298.15 K. The solvent's ensemble free energy is

Gsensemble=−RTln⁡∑iexp⁡(−Gi,sRT).G_s^{\mathrm{ensemble}} = -RT\ln\sum_i \exp\left(-\frac{G_{i,s}}{RT}\right).

Settings

By default, the workflow evaluates hexane, octanol, chloroform, dimethyl sulfoxide (DMSO), and water. You can select a different subset of supported solvents, adjust the conformer generator and its energy window, configure the multistage optimization, and choose CPCM-X or COSMO-RS as the final correction.

COSMO-RS supports the solvents bundled with the workflow and molecules containing elements for which the COSMO-RS cavity model has radii. Unsupported solvents or elements should use the CPCM-X route instead.

Results

The workflow returns the retained conformers and, for each solvent, their free energies and Boltzmann populations. It also reports Boltzmann-averaged solvent-accessible surface area, polar solvent-accessible surface area, and radius of gyration, together with each solvent's relative ensemble free energy. These results show both which structures dominate in each environment and how the overall ensemble changes between solvents.