Conformational searching is the task of figuring out what the low-energy structures of a given molecule will be. Since the shape of a molecule determines what downstream activity it will have when interacting with a target, like a protein or membrane, conformational searching is an important and foundational task in computational chemistry and in silico modeling.
Since the number of potential conformers grows exponentially with the number of rotatable bonds, efficient and performant conformer searching requires judicious use of screening and filtering to avoid wasting time computing high-energy conformers that will be discarded.
Typical conformational search workflows link together two or three computational chemistry programs: conformers are first generated and scored using a quick and inaccurate level of theory, and then iterative rounds of refinement and reoptimization are applied to eliminate high-energy conformers and generate the final ensemble. This multi-level approach, while computationally efficient, requires users to be comfortable with a variety of different software, and necessitates manual scripting or resubmission between each layer.
Rowan's conformer search workflow makes accurate and efficient conformational searching easy. Starting from a variety of molecular representations, including SMILES strings, you can select from four different levels of theory ("reckless", "rapid", "careful", or "meticulous"), choose the solvent in which you want to score the conformers, and then submit the search!
The entire multi-level conformational search will run automatically following established best practices: Rowan uses a number of techniques to eliminate redundant conformers, including screens for "trivial" conformational changes like bond rotations and cutoff-based methods to make sure virtually identical conformers aren't included in the final ensemble. By default, fast and accurate machine-learned interatomic potentials are used for the final optimization, making Rowan's workflow far more efficient than conventional quantum chemistry-based workflows.
Here's the output of a conformational search in Rowan:
Rowan automatically calculates the Boltzmann weight associated with each conformer and sorts the conformational ensemble, so you can quickly see how abundant each conformer is. You can also superimpose all conformers by clicking "Overlay all conformers," which gives a single publication-quality visualization of the entire ensemble; this overlay can be aligned to specific fragments by selecting these atoms in the viewer.
Rowan's conformational search workflow works on a wide variety of compounds: cations, anions, free radicals, transition metals, and even lanthanides! (Here's a conformational search we ran on a Dysprosium-containing macrocycle.) Rowan also allows for arbitrary geometric constraints to be applied to conformational searches, which makes it possible to run conformational searches on supramolecular complexes, transition states, and more.
