• About
• Install
• Concept
• Examples
• Citation

The code runs on pure python with the following dependencies:

• numpy
• scipy
• matplotlib
• scikit-learn
• networkx

You can install marc using pip:

pip install navicat_marc

Afterwards, you can call marc as:

python -m navicat_marc [-h] [-version] -i INPUT [INPUT ...] [-c C] [-m M] [-n N] [-ewin EWIN] [-sf SF] [-mine] [-yesh] [-s] [-nosymm] [-as] [-efile EFILE] [-v VERB] [-pm PLOTMODE]

or simply

navicat_marc [-h] [-version] -i INPUT [INPUT ...] [-c C] [-m M] [-n N] [-ewin EWIN] [-sf SF] [-mine] [-yesh] [-s] [-nosymm] [-as] [-efile EFILE] [-v VERB] [-pm PLOTMODE]

Alternatively, you can download the package and execute:

python setup.py install

or

pip install .

Options can be consulted using the -h flag in either case. The help menu is quite detailed.

Note that the main functions are all exposed and called directly in sequential order from marc.py, in case you want to incorporate them in your own code.

Several strategies are available for the generation of conformational ensembles. Typically, one then needs to sort the ensemble and proceed with the study of the most energetically favored conformers, which will be the most accesible thermodynamically following a Boltzmann distribution.

However, sorting conformers accurately requires high quality energy computations. Accurately determining the energy of every structure may be too computationally demanding. Furthermore, upon refinement many conformers may collapse to the same stationary point. Even worse, for some tasks, knowledge of conformer interconvertibility is highly important.

To untangle these issues, marc provides a convenient way of accomplishing three goals:

• Select a handful of distinct conformers that are representative of the diversity of the conformational ensemble using combined metrics.
• Apply energy cutoffs based on the available energies to remove entire clusters from the space using the -ewin flag and inputting a treshold in kcal/mol.
• Proceed iteratively, helping the user select non-redundant conformers than can then be refined with a higher level and fed back to marc.

The default clustering metric used in marc is the "avg" distance, which measures pairwise similarity based on the average of three normalized distance matrices: heavy-atom rmsd, energy difference and kernel of the heavy-atom dihedral angles of the system.

The logic behind this choice is that rmsd ought to be good except in cases where trivial single bond rotations increase the rmsd without affecting the energy, while the dihedral metric smooths systems that only differ by a few torsions. The possible metrics (to be fed to the -m flag) are "rmsd", "erel" (based on the available energies), "da" (based on the most relevant dihedral angle of the molecule), "ewrmsd" (combining geometry and energy) and "mix" (combining geometry, dihedrals and energy with the DISTATIS algorithm), other than the default avg.

The examples subdirectory contains some examples obtained by running CREST. Any of the xyz files can be run as:

navicat_marc -i [FILENAME]

Options can be consulted with the -h flag.

The input of marc is either a series or xyz files or a single trajectory-like xyz file with many conformers. All structures are expected to be analogous in terms of sorting and molecular topology. Energies per conformer, at any level of theory of your liking but in atomic units, can be provided in atomic units in the title line of each xyz block or file. Alternatively, energies can be provided in a plaintext file whose filename can be passed to the ewin command line argument. Such file must contain the same number of lines as conformers and two numbers per line (separated by blank spaces): an index, and an energy in atomic units. The energy window specified in the ewin command line argument should be in kcal/mol.

Note that, by default, marc will select the most representative conformer out of every cluster. If you can provide energy values that you trust strongly, the mine flag will ensure that the lowest energy conformer of every cluster is selected.

The output of marc are n selected xyz files which will be called INPUT_selected_n.xyz in the runtime directory. Conformers discarded by the ewin threshold will be printed with the rejected appendix instead. The discarding checks two criteria: if a cluster has an average energy that is mine kcal/mol higher than the lowest conformer (plus half a standard deviation), and its lowest energy member is also higher than the threshold, the entire cluster will be discarded.

High verbosity levels (-v 1, -v 2, etc.) will print significantly more information while marc runs. To be as automated as possible, reasonable default values are set for most choices, but extreme verbosity can be obtained by raising the value.

marc is able to use molecular symmetry and deal with shuffling, including the effect of bond rotations and symmetries, when computing heavy atom rmsd. However, this comes at a cost, and therefore this function is deactivated automatically for large systems. You can enfoce sorting by including the flags -s and -as, where s uses an approximate sorting routine and as does brute force rmsd comparisons over isomorphisms. nosymm deactivates this functionality, which can lead to wrong rmsds! Luckily, you can always resort to metrics that do not require rmsd.

As a final note, marc does not consider hydrogen atoms for geometry analysis. You can force marc to include them by using the -yesh flag, which is generally not recommended. Obviously, including hydrogens makes any sorting much more time consuming.

Please cite our work with the repository DOI and the manuscript that introduced the code. You can find it here and in the reference:

Laplaza, R.; Wodrich, M. D.; Corminboeuf, C. Overcoming the Pitfalls of Computing Reaction Selectivity from Ensembles of Transition States. J. Phys. Chem. Lett. 2024, 15 (29), 7363–7370. https://doi.org/10.1021/acs.jpclett.4c01657.