Molecules with rotatable bonds can exist in multiple conformations, and locating the lowest energy conformation is crucial for ensuring the accuracy of subsequent tasks. Running a conformational search can also reveal the conformational preferences of different bonds, and show how strained various alternate conformations are relative to the global minimum. Rowan's conformational searching workflow uses fast low-level methods to explore conformational space, followed by more accurate machine-learned interatomic potentials to score the poses generated.
Conformers are generated using either RDKit's ETKDG algorithm or the CREST iterative metadynamics search program. The low-energy conformers are collected and optimized using AIMNet2, and the gas-phase Gibbs free energy from AIMNet2 is combined with CPCM-X aqueous solvation free energy predictions from GFN2-xTB to yield a final solvated free energy for each conformer. Rowan ranks and scores the conformers, printing the corresponding Boltzmann weight to enable easy downstream analysis.
Rowan's conformer workflow can be run in four modes: meticulous, careful, rapid, or reckless. Here's what selecting each mode tunes:
| Mode | Meticulous | Careful | Rapid | Reckless |
|---|---|---|---|---|
| program used for conformer generation | CREST | CREST | RDKit | RDKit |
| level of theory used for conformer generation | GFN2-xTB | GFN-FF | MMFF | MMFF |
| mode (CREST) | normal | quick | ||
| number of initial conformations (ETKDG) | 300 | 200 | ||
| initial energy cutoff (kcal/mol) | 15 | 10 | 15 | 10 |
| RMSD similarity cutoff (Ã…) | 0.00 | 0.00 | 0.10 | 0.25 |
| max number of conformers (xTB) | 500 | 150 | 100 | 50 |
| final energy cutoff (kcal/mol) | 10 | 5 | 5 | 5 |
| max number of conformers (AIMNet2) | 150 | 50 | 50 | 20 |
In general, the "rapid" mode provides a good balance between speed and accuracy for most applications.