Introduction

The main purpose of fragmenter is to fragment molecules for quantum chemical (QC) torsion drives. Since fragmenter is part of the Open Force Field echo system, it also includes other functionality to automate other aspects of the torsion fitting pipeline such as enumerating reasonable tautomers, finding the torsions to drive, generating starting conformations for QC torsion drives and generating JSON input for submission to QCArchive.

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. 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.

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, 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. Stern C.D., Smith D.G.A, Bayly C.I., Chodera J.D Fragmenting molecules for QC torsion drives doi 10.5281/zenodo.3238643