Tuesday 18 February 2020

Reflecting on stereochemistry

Stereochemistry is a tricky concept. And writing programs to handle it is equally tricky. Take tetrahedral stereochemistry for example; it's 'interesting' to note that none of the following markers of parity use the same system: R/S in IUPAC names, D/L in biochemical nomenclature, @/@@ in SMILES, atom parity flag 1/2 in MOL files, or InChI's +/-. Which is why a sane cheminformatics library abstracts the representation of stereochemistry away from any one format to one which can be more easily reasoned about and interconverted to all.

Here's the introduction to a description I wrote up last week of how stereochemistry is handled in Open Babel. In particular, it tries to make clear how the different aspects of stereochemistry information (e.g. coordinates versus stereochemical configurations perceived from those coordinates) interact with each other from the point of view of the toolkit.

Open Babel stores stereochemistry as the relative arrangement of a set of atoms in space. For example, for a tetrahedral stereocenter, we store information like “looking from atom 2, atoms 4, 5 and 6 are arranged clockwise around atom 3”. This section describes how a user can work with or manipulate this information. This might be useful to invert a particular center, replace a substituent at a stereocenter, enumerate stereoisomers or determine the number of unspecified stereocenters.

Although Open Babel has data structures to support a variety of forms of stereochemistry, currently little use is made of any stereochemistry other than tetrahedral and cis/trans (and square planar to a certain degree).

We will look first of all at how stereochemistry information is stored, accessed, and modified. Then we describe how this information is deduced from the chemical structure. This chapter should be read in combination with the API documentation (see the Stereochemistry overview page found under “Modules”)...

The full version can be found in the development docs. Thanks to Geoff Hutchison and Stefano Forli for feedback on an early draft.

Image credit: Monument to Paul Walden by Anita Gould (licensed CC-BY-NC)