Chemical similarity

Currently pondering how to quantify chemical similarity, based on SMILES or InChI strings representing any given two chemicals / metabolites.

I've had a little play with the rather good Chemical Development Kit (CDK), developed by Egon Wilighagen and Christoph Steinbeck and have hit a bit of a brick wall.

Consider the following reaction:

In this case, I'd like to quantify the similarity between glucose and glucose 6-phosphate.

My first approach was to use the CDK's ExtendedFingerprinter class to generate a BitSet representation of each molecule, and then generate a Tanimoto coefficient which should quantify similarity:

String smiles1 = 

"

OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O";

String smiles2 = 

"

O[C@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O";

IAtomContainer molecule1 = smilesParser.parseSmiles( 

smiles1 

);

IAtomContainer molecule2 = smilesParser.parseSmiles( smiles2

 );

ExtendedFingerprinter ef = new ExtendedFingerprinter();

BitSet fingerprint1 = ef.getFingerprint( molecule1 );

BitSet fingerprint2 = 

ef.getFingerprint( molecule2 );

float tanimotoCoefficient = Tanimoto.calculate( fingerprint1, fingerprint2 );

System.out.println( tanimotoCoefficient );

In this case, a "similarity score" of 0.475 is calculated, which intuitively I find a little low, given how much of the structure is shared.

I'm assuming (using a sequence analysis analogy) that the Tanimoto coefficient is a measure of global similarity. What I'm after here, I suppose, is a measure of local similarity - effectively something that can quantify the fact that we can pretty much map the entire structure of glucose onto that of glucose 6-phosphate.

I understand that elsewhere in the CDK, the UniversalIsomorphismTester class may be more appropriate. Does anyone have any experience of this?

Any help would be appreciated!