Algorithm used by PubChem to determine the 2D layout assignment for Compound entries?
According to Xemistry, PubChem uses Cactvs for 2D layout coordinate computation.
A friend pointed this out to me. If you scroll to the bottom of the CACTVS Toolkit FAQ (http://www.xemistry.com/docs.htm), it says the following:

Interesting. I did not know that PubChem is built with Cactvs. I heard it was implemented with OpenEye's OEChem library.
Well, that is not wrong, but only part of the story. Both Cactvs and OpenEye software are used, in combination with the in-house NCBI toolkit. Software built with Cactvs is in charge of structure submission pre-parsing, structure input, structure ASN.1 encoding, 2D layout coordinate computation, structure rendering, most property computations, structure unification, the complete structure search system and Web-based structure sketching for queries. The OpenEye toolkit is used for structure standardization, some property computation (names, canonic SMILES), and SD file output. There are applications at NCBI which link to both OpenEye and Xemistry libraries - they can peacefully co-exist.