# OpenFF Fragmenter¶

The main purpose of openff-fragmenter is to fragment molecules for quantum chemical (QC) torsion drives.

Warning

openff-fragmenter is still pre-alpha. It is not fully tested and the API is still in flux.

Currently two fragmentation schemes are supported:

• a Wiberg Bond Order (WBO) sensitive fragmentation scheme [1] (recommended)

• the fragmentation schema detailed by Rai et al [2] reffered to in this package as the ‘Pfizer’ scheme.

## WBO Sensitive Fragmentation¶

The assumption when fragmenting molecules is that the chemistry is localized and that removing or changing remote substituents (defined as substituents more than 2 bonds away from the central bond that is being driven in the torsion drive) will not change the torsion potential around the bond of interest. However, that is not always the case. openff-fragmenter uses the Wiberg Bond Order (WBO) as a surrogate signal to determine if the chemistry around the bond of interest was destroyed during fragmentation relative to the bond in the parent molecule.

The WBO is a measure of electronic population overlap between two atoms in a bond. It can be quickly calculated from an empirical QC calculation and is given by:

$W_{AB} = \sum_{\mu\in{A}}\sum_{\nu\in{B}}|D_{\mu\nu}|^2$

Where $$A$$ and $$B$$ are atoms $$A$$ and $$B$$ in a bond, $$D$$ is the density matrix and $$\mu$$ and $$\nu$$ are occupied orbitals on atoms $$A$$ and $$B$$ respectively.

openff-fragmenter calculates the WBO of the parent molecules, then fragments according to a set of rules and then recalculates the WBO of the fragments. If the WBO for the fragment of the bond of interest changes more than a user’s specified threshold, openff-fragmenter will add more substituents until the WBO of the bond of interest is within the user specified threshold.

## Acknowledgment¶

CDS is funded by a fellowship from The Molecular Sciences Software Institute

## References¶

1

Chaya D Stern, Christopher I Bayly, Daniel G A Smith, Josh Fass, Lee-Ping Wang, David L Mobley, and John D Chodera. Capturing non-local through-bond effects when fragmenting molecules for quantum chemical torsion scans. bioRxiv, 2020. URL: https://www.biorxiv.org/content/early/2020/08/28/2020.08.27.270934, arXiv:https://www.biorxiv.org/content/early/2020/08/28/2020.08.27.270934.full.pdf, doi:10.1101/2020.08.27.270934.

2

Brajesh K. Rai, Vishnu Sresht, Qingyi Yang, Ray Unwalla, Meihua Tu, Alan M. Mathiowetz, and Gregory A. Bakken. Comprehensive assessment of torsional strain in crystal structures of small molecules and protein–ligand complexes using ab initio calculations. Journal of Chemical Information and Modeling, 59(10):4195–4208, 2019. PMID: 31573196. URL: https://doi.org/10.1021/acs.jcim.9b00373, arXiv:https://doi.org/10.1021/acs.jcim.9b00373, doi:10.1021/acs.jcim.9b00373.